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1. p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Author: Köbel, Martin, Köbel, Martin, Kang, Eun‐Young, Weir, Ashley, Rambau, Peter F, Lee, Cheng‐Han, Nelson, Gregg S, Ghatage, Prafull, Meagher, Nicola S, Riggan, Marjorie J, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Bisinotto, Christiani, Boisen, Michelle, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Carney, Michael E, Coulson, Penny, Courtney‐Brooks, Madeleine, Cushing‐Haugen, Kara L, Cybulski, Cezary, Deen, Suha, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Group, AOCS, Fischer, Anna, Gayther, Simon A, Barquin‐Garcia, Arantzazu, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Gronwald, Helena, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartkopf, Andreas D, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Huang, Yajue, Jakubowska, Anna, Jimenez‐Linan, Mercedes, Jones, Michael E, Kennedy, Catherine J, Kluz, Tomasz, Koziak, Jennifer M, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Longacre, Teri A, Lycke, Maria, Mateoiu, Constantina, McCauley, Bryan M, McGuire, Valerie, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Paz‐Ares, Luis, Ramón y Cajal, Teresa, Rothstein, Joseph H, Ruebner, Matthias, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Sherman, Mark E, Shvetsov, Yurii B, Singh, Naveena, Steed, Helen, Storr, Sarah J, Talhouk, Aline, Traficante, Nadia, Wang, Chen, Whittemore, Alice S, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, dos Reis, Francisco J Candido, Campbell, Ian, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Fasching, Peter A, Fortner, Renée T, García, María J, Goodman, Marc T, Goode, Ellen L, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kelemen, Linda E, Kommoss, Stefan, Le, Nhu D, Martin, Stewart G, Köbel, Martin, Köbel, Martin, Kang, Eun‐Young, Weir, Ashley, Rambau, Peter F, Lee, Cheng‐Han, Nelson, Gregg S, Ghatage, Prafull, Meagher, Nicola S, Riggan, Marjorie J, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Bisinotto, Christiani, Boisen, Michelle, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Carney, Michael E, Coulson, Penny, Courtney‐Brooks, Madeleine, Cushing‐Haugen, Kara L, Cybulski, Cezary, Deen, Suha, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Group, AOCS, Fischer, Anna, Gayther, Simon A, Barquin‐Garcia, Arantzazu, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Gronwald, Helena, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartkopf, Andreas D, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Huang, Yajue, Jakubowska, Anna, Jimenez‐Linan, Mercedes, Jones, Michael E, Kennedy, Catherine J, Kluz, Tomasz, Koziak, Jennifer M, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Longacre, Teri A, Lycke, Maria, Mateoiu, Constantina, McCauley, Bryan M, McGuire, Valerie, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Paz‐Ares, Luis, Ramón y Cajal, Teresa, Rothstein, Joseph H, Ruebner, Matthias, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Sherman, Mark E, Shvetsov, Yurii B, Singh, Naveena, Steed, Helen, Storr, Sarah J, Talhouk, Aline, Traficante, Nadia, Wang, Chen, Whittemore, Alice S, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, dos Reis, Francisco J Candido, Campbell, Ian, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Fasching, Peter A, Fortner, Renée T, García, María J, Goodman, Marc T, Goode, Ellen L, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kelemen, Linda E, Kommoss, Stefan, Le, Nhu D, and Martin, Stewart G
Abstract: Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
Published: 2023

2. Profiling the immune landscape in mucinous ovarian carcinoma.

Author: Meagher, Nicola, Meagher, Nicola, Hamilton, Phineas, Milne, Katy, Thornton, Shelby, Harris, Bronwyn, Weir, Ashley, Alsop, Jennifer, Bisinoto, Christiani, Brenton, James, Brooks-Wilson, Angela, Chiu, Derek, Cushing-Haugen, Kara, Fereday, Sian, Garsed, Dale, Gayther, Simon, Gentry-Maharaj, Aleksandra, Gilks, Blake, Jimenez-Linan, Mercedes, Kennedy, Catherine, Le, Nhu, Piskorz, Anna, Riggan, Marjorie, Shah, Mitul, Singh, Naveena, Talhouk, Aline, Widschwendter, Martin, Bowtell, David, Candido Dos Reis, Francisco, Cook, Linda, Fortner, Renée, García, María, Harris, Holly, Huntsman, David, Köbel, Martin, Menon, Usha, Pharoah, Paul, Doherty, Jennifer, Anglesio, Michael, Pike, Malcolm, Pearce, Celeste, Friedlander, Michael, DeFazio, Anna, Nelson, Brad, Ramus, Susan, Karnezis, Anthony, Meagher, Nicola, Meagher, Nicola, Hamilton, Phineas, Milne, Katy, Thornton, Shelby, Harris, Bronwyn, Weir, Ashley, Alsop, Jennifer, Bisinoto, Christiani, Brenton, James, Brooks-Wilson, Angela, Chiu, Derek, Cushing-Haugen, Kara, Fereday, Sian, Garsed, Dale, Gayther, Simon, Gentry-Maharaj, Aleksandra, Gilks, Blake, Jimenez-Linan, Mercedes, Kennedy, Catherine, Le, Nhu, Piskorz, Anna, Riggan, Marjorie, Shah, Mitul, Singh, Naveena, Talhouk, Aline, Widschwendter, Martin, Bowtell, David, Candido Dos Reis, Francisco, Cook, Linda, Fortner, Renée, García, María, Harris, Holly, Huntsman, David, Köbel, Martin, Menon, Usha, Pharoah, Paul, Doherty, Jennifer, Anglesio, Michael, Pike, Malcolm, Pearce, Celeste, Friedlander, Michael, DeFazio, Anna, Nelson, Brad, Ramus, Susan, and Karnezis, Anthony
Abstract: OBJECTIVE: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION: In summary, MOCs are mostly immunogenically cold, suggesting they may have limited response to current immunotherapies.
Published: 2023

3. Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

Author: Weir, Ashley, Weir, Ashley, Kang, Eun-Young, Meagher, Nicola S, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Gentry-Maharaj, Aleksandra, Ryan, Andy, Singh, Naveena, Widschwendter, Martin, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Boros, Jessica, Brand, Alison H, Brenton, James D, Brooks-Wilson, Angela, Carney, Michael E, Cunningham, Julie M, Cushing-Haugen, Kara L, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Fischer, Anna, Paz-Ares, Luis, Gayarre, Javier, Gilks, Blake C, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Heublein, Sabine, Huang, Yajue, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kommoss, Felix KF, Koziak, Jennifer M, Kraemer, Bernhard, Le, Nhu D, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Menkiszak, Janusz, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Robles-Díaz, Luis, Ruebner, Matthias, Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B, Steed, Helen, Talhouk, Aline, Taylor, Sarah E, Traficante, Nadia, Vierkant, Robert A, Wang, Chen, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, Candido Dos Reis, Francisco J, Cook, Linda S, DeFazio, Anna, AOCs group, Doherty, Jennifer A, Fasching, Peter A, García, María J, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kommoss, Stefan, Modugno, Francesmary, Schildkraut, Joellen M, Sinn, Hans-Peter, Staebler, Annette, Kelemen, Linda E, Ford, Caroline E, Menon, Usha, Pharoah, Paul DP, Köbel, Martin, Ramus, Susan J, Weir, Ashley, Weir, Ashley, Kang, Eun-Young, Meagher, Nicola S, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Gentry-Maharaj, Aleksandra, Ryan, Andy, Singh, Naveena, Widschwendter, Martin, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Boros, Jessica, Brand, Alison H, Brenton, James D, Brooks-Wilson, Angela, Carney, Michael E, Cunningham, Julie M, Cushing-Haugen, Kara L, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Fischer, Anna, Paz-Ares, Luis, Gayarre, Javier, Gilks, Blake C, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Heublein, Sabine, Huang, Yajue, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kommoss, Felix KF, Koziak, Jennifer M, Kraemer, Bernhard, Le, Nhu D, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Menkiszak, Janusz, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Robles-Díaz, Luis, Ruebner, Matthias, Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B, Steed, Helen, Talhouk, Aline, Taylor, Sarah E, Traficante, Nadia, Vierkant, Robert A, Wang, Chen, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, Candido Dos Reis, Francisco J, Cook, Linda S, DeFazio, Anna, AOCs group, Doherty, Jennifer A, Fasching, Peter A, García, María J, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kommoss, Stefan, Modugno, Francesmary, Schildkraut, Joellen M, Sinn, Hans-Peter, Staebler, Annette, Kelemen, Linda E, Ford, Caroline E, Menon, Usha, Pharoah, Paul DP, Köbel, Martin, and Ramus, Susan J
Abstract: BackgroundRecently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.MethodsTwo prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.ResultsConsistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant.ConclusionWe provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.
Published: 2023

4. Endometrial carcinosarcoma

Author: Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, Mccormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, Monk, Bradley J, Scambia, Giovanni (ORCID:0000-0003-2758-1063), Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, Mccormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, Monk, Bradley J, and Scambia, Giovanni (ORCID:0000-0003-2758-1063)
Abstract: Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.
Published: 2023

5. Endometrial carcinosarcoma

Author: Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Caruso, G, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Póka, R, Segev, Y, Kim, S, Kim, J, Candido Dos Reis, F, Ramirez, P, Mariani, A, Leitao, M, Makker, V, Abu-Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Paolini, B, Bini, M, Raspagliesi, F, Benedetti Panici, P, Di Donato, V, Muzii, L, Colombo, N, Pignata, S, Scambia, G, Monk, B, Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, McCormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, Monk, Bradley J, Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Caruso, G, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Póka, R, Segev, Y, Kim, S, Kim, J, Candido Dos Reis, F, Ramirez, P, Mariani, A, Leitao, M, Makker, V, Abu-Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Paolini, B, Bini, M, Raspagliesi, F, Benedetti Panici, P, Di Donato, V, Muzii, L, Colombo, N, Pignata, S, Scambia, G, Monk, B, Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, McCormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, and Monk, Bradley J
Abstract: Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.
Published: 2023

6. MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma.

Author: Kang, Eun Young, Kang, Eun Young, Millstein, Joshua, Popovic, Gordana, Meagher, Nicola S, Bolithon, Adelyn, Talhouk, Aline, Chiu, Derek S, Anglesio, Michael S, Leung, Betty, Tang, Katrina, Lambie, Neil, Pavanello, Marina, Da-Anoy, Annalyn, Lambrechts, Diether, Loverix, Liselore, Olbrecht, Siel, Bisinotto, Christiani, Garcia-Donas, Jesus, Ruiz-Llorente, Sergio, Yagüe-Fernandez, Monica, Edwards, Robert P, Elishaev, Esther, Olawaiye, Alexander, Taylor, Sarah, Ataseven, Beyhan, du Bois, Andreas, Harter, Philipp, Lester, Jenny, Høgdall, Claus K, Armasu, Sebastian M, Huang, Yajue, Vierkant, Robert A, Wang, Chen, Winham, Stacey J, Heublein, Sabine, Kommoss, Felix KF, Cramer, Daniel W, Sasamoto, Naoko, van-Wagensveld, Lilian, Lycke, Maria, Mateoiu, Constantina, Joseph, Janine, Pike, Malcolm C, Odunsi, Kunle, Tseng, Chiu-Chen, Pearce, Celeste L, Bilic, Sanela, Conrads, Thomas P, Hartmann, Arndt, Hein, Alexander, Jones, Michael E, Leung, Yee, Beckmann, Matthias W, Ruebner, Matthias, Schoemaker, Minouk J, Terry, Kathryn L, El-Bahrawy, Mona A, Coulson, Penny, Etter, John L, LaVigne-Mager, Katherine, Andress, Juergen, Grube, Marcel, Fischer, Anna, Neudeck, Nina, Robertson, Greg, Farrell, Rhonda, Barlow, Ellen, Quinn, Carmel, Hettiaratchi, Anusha, Casablanca, Yovanni, Erber, Ramona, Stewart, Colin JR, Tan, Adeline, Yu, Yu, Boros, Jessica, Brand, Alison H, Harnett, Paul R, Kennedy, Catherine J, Nevins, Nikilyn, Morgan, Terry, Fasching, Peter A, Vergote, Ignace, Swerdlow, Anthony J, Candido Dos Reis, Francisco J, Maxwell, G Larry, Neuhausen, Susan L, Barquin-Garcia, Arantzazu, Modugno, Francesmary, Moysich, Kirsten B, Crowe, Philip J, Hirasawa, Akira, Heitz, Florian, Karlan, Beth Y, Goode, Ellen L, Sinn, Peter, Horlings, Hugo M, Høgdall, Estrid, Sundfeldt, Karin, Kommoss, Stefan, Staebler, Annette, Kang, Eun Young, Kang, Eun Young, Millstein, Joshua, Popovic, Gordana, Meagher, Nicola S, Bolithon, Adelyn, Talhouk, Aline, Chiu, Derek S, Anglesio, Michael S, Leung, Betty, Tang, Katrina, Lambie, Neil, Pavanello, Marina, Da-Anoy, Annalyn, Lambrechts, Diether, Loverix, Liselore, Olbrecht, Siel, Bisinotto, Christiani, Garcia-Donas, Jesus, Ruiz-Llorente, Sergio, Yagüe-Fernandez, Monica, Edwards, Robert P, Elishaev, Esther, Olawaiye, Alexander, Taylor, Sarah, Ataseven, Beyhan, du Bois, Andreas, Harter, Philipp, Lester, Jenny, Høgdall, Claus K, Armasu, Sebastian M, Huang, Yajue, Vierkant, Robert A, Wang, Chen, Winham, Stacey J, Heublein, Sabine, Kommoss, Felix KF, Cramer, Daniel W, Sasamoto, Naoko, van-Wagensveld, Lilian, Lycke, Maria, Mateoiu, Constantina, Joseph, Janine, Pike, Malcolm C, Odunsi, Kunle, Tseng, Chiu-Chen, Pearce, Celeste L, Bilic, Sanela, Conrads, Thomas P, Hartmann, Arndt, Hein, Alexander, Jones, Michael E, Leung, Yee, Beckmann, Matthias W, Ruebner, Matthias, Schoemaker, Minouk J, Terry, Kathryn L, El-Bahrawy, Mona A, Coulson, Penny, Etter, John L, LaVigne-Mager, Katherine, Andress, Juergen, Grube, Marcel, Fischer, Anna, Neudeck, Nina, Robertson, Greg, Farrell, Rhonda, Barlow, Ellen, Quinn, Carmel, Hettiaratchi, Anusha, Casablanca, Yovanni, Erber, Ramona, Stewart, Colin JR, Tan, Adeline, Yu, Yu, Boros, Jessica, Brand, Alison H, Harnett, Paul R, Kennedy, Catherine J, Nevins, Nikilyn, Morgan, Terry, Fasching, Peter A, Vergote, Ignace, Swerdlow, Anthony J, Candido Dos Reis, Francisco J, Maxwell, G Larry, Neuhausen, Susan L, Barquin-Garcia, Arantzazu, Modugno, Francesmary, Moysich, Kirsten B, Crowe, Philip J, Hirasawa, Akira, Heitz, Florian, Karlan, Beth Y, Goode, Ellen L, Sinn, Peter, Horlings, Hugo M, Høgdall, Estrid, Sundfeldt, Karin, Kommoss, Stefan, and Staebler, Annette
Abstract: Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
Published: 2022

7. Clear cell carcinoma of the endometrium

Author: Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Y L, Morice, Philippe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco J, Mariani, Andrea, Leitao, Mario M, Makker, Viky, Rustum, Nadeem Abu, Vergote, Ignace, Zannoni, Gian Franco, Tan, David S P, Mccormack, Mary, Bini, Marta, Lopez, Salvatore, Raspagliesi, Francesco, Panici, Pierluigi Benedetti, di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Scambia, Giovanni, Pignata, Sandro, Monk, Bradley J, Zannoni, Gian Franco (ORCID:0000-0003-1809-129X), Scambia, Giovanni (ORCID:0000-0003-2758-1063), Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Y L, Morice, Philippe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco J, Mariani, Andrea, Leitao, Mario M, Makker, Viky, Rustum, Nadeem Abu, Vergote, Ignace, Zannoni, Gian Franco, Tan, David S P, Mccormack, Mary, Bini, Marta, Lopez, Salvatore, Raspagliesi, Francesco, Panici, Pierluigi Benedetti, di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Scambia, Giovanni, Pignata, Sandro, Monk, Bradley J, Zannoni, Gian Franco (ORCID:0000-0003-1809-129X), and Scambia, Giovanni (ORCID:0000-0003-2758-1063)
Abstract: Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma. (C) 2022 Elsevier Inc. All rights reserved.
Published: 2022

8. MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma

Author: Kang, Eun Young, Millstein, Joshua, Popovic, Gordana, Meagher, Nicola S., Bolithon, Adelyn, Talhouk, Aline, Chiu, Derek S., Anglesio, Michael S., Leung, Betty, Tang, Katrina, Lambie, Neil, Pavanello, Marina, Da-anoy, Annalyn, Lambrechts, Diether, Loverix, Liselore, Olbrecht, Siel, Bisinotto, Christiani, Garcia-Donas, Jesus, Ruiz-Llorente, Sergio, Yagüe-Fernandez, Monica, Edwards, Robert P., Elishaev, Esther, Olawaiye, Alexander, Taylor, Sarah, Ataseven, Beyhan, du Bois, Andreas, Harter, Philipp, Lester, Jenny, Høgdall, Claus K., Armasu, Sebastian M., Huang, Yajue, Vierkant, Robert A., Wang, Chen, Winham, Stacey J., Heublein, Sabine, Kommoss, Felix K.F., Cramer, Daniel W., Sasamoto, Naoko, van-Wagensveld, Lilian, Lycke, Maria, Mateoiu, Constantina, Joseph, Janine, Pike, Malcolm C., Odunsi, Kunle, Tseng, Chiu Chen, Pearce, Celeste L., Bilic, Sanela, Conrads, Thomas P., Hartmann, Arndt, Hein, Alexander, Jones, Michael E., Leung, Yee, Beckmann, Matthias W., Ruebner, Matthias, Schoemaker, Minouk J., Terry, Kathryn L., El-Bahrawy, Mona A., Coulson, Penny, Etter, John L., LaVigne-Mager, Katherine, Andress, Juergen, Grube, Marcel, Fischer, Anna, Neudeck, Nina, Robertson, Greg, Farrell, Rhonda, Barlow, Ellen, Quinn, Carmel, Hettiaratchi, Anusha, Casablanca, Yovanni, Erber, Ramona, Stewart, Colin J.R., Tan, Adeline, Yu, Yu, Boros, Jessica, Brand, Alison H., Harnett, Paul R., Kennedy, Catherine J., Nevins, Nikilyn, Morgan, Terry, Fasching, Peter A., Vergote, Ignace, Swerdlow, Anthony J., Candido dos Reis, Francisco J., Maxwell, G. Larry, Neuhausen, Susan L., Barquin-Garcia, Arantzazu, Modugno, Francesmary, Moysich, Kirsten B., Crowe, Philip J., Hirasawa, Akira, Heitz, Florian, Karlan, Beth Y., Goode, Ellen L., Sinn, Peter, Horlings, Hugo M., Høgdall, Estrid, Sundfeldt, Karin, Kommoss, Stefan, Staebler, Annette, Wu, Anna H., Cohen, Paul A., DeFazio, Anna, Lee, Cheng Han, Steed, Helen, Le, Nhu D., Gayther, Simon A., Lawrenson, Kate, Pharoah, Paul D.P., Konecny, Gottfried, Cook, Linda S., Ramus, Susan J., Kelemen, Linda E., Köbel, Martin, Kang, Eun Young, Millstein, Joshua, Popovic, Gordana, Meagher, Nicola S., Bolithon, Adelyn, Talhouk, Aline, Chiu, Derek S., Anglesio, Michael S., Leung, Betty, Tang, Katrina, Lambie, Neil, Pavanello, Marina, Da-anoy, Annalyn, Lambrechts, Diether, Loverix, Liselore, Olbrecht, Siel, Bisinotto, Christiani, Garcia-Donas, Jesus, Ruiz-Llorente, Sergio, Yagüe-Fernandez, Monica, Edwards, Robert P., Elishaev, Esther, Olawaiye, Alexander, Taylor, Sarah, Ataseven, Beyhan, du Bois, Andreas, Harter, Philipp, Lester, Jenny, Høgdall, Claus K., Armasu, Sebastian M., Huang, Yajue, Vierkant, Robert A., Wang, Chen, Winham, Stacey J., Heublein, Sabine, Kommoss, Felix K.F., Cramer, Daniel W., Sasamoto, Naoko, van-Wagensveld, Lilian, Lycke, Maria, Mateoiu, Constantina, Joseph, Janine, Pike, Malcolm C., Odunsi, Kunle, Tseng, Chiu Chen, Pearce, Celeste L., Bilic, Sanela, Conrads, Thomas P., Hartmann, Arndt, Hein, Alexander, Jones, Michael E., Leung, Yee, Beckmann, Matthias W., Ruebner, Matthias, Schoemaker, Minouk J., Terry, Kathryn L., El-Bahrawy, Mona A., Coulson, Penny, Etter, John L., LaVigne-Mager, Katherine, Andress, Juergen, Grube, Marcel, Fischer, Anna, Neudeck, Nina, Robertson, Greg, Farrell, Rhonda, Barlow, Ellen, Quinn, Carmel, Hettiaratchi, Anusha, Casablanca, Yovanni, Erber, Ramona, Stewart, Colin J.R., Tan, Adeline, Yu, Yu, Boros, Jessica, Brand, Alison H., Harnett, Paul R., Kennedy, Catherine J., Nevins, Nikilyn, Morgan, Terry, Fasching, Peter A., Vergote, Ignace, Swerdlow, Anthony J., Candido dos Reis, Francisco J., Maxwell, G. Larry, Neuhausen, Susan L., Barquin-Garcia, Arantzazu, Modugno, Francesmary, Moysich, Kirsten B., Crowe, Philip J., Hirasawa, Akira, Heitz, Florian, Karlan, Beth Y., Goode, Ellen L., Sinn, Peter, Horlings, Hugo M., Høgdall, Estrid, Sundfeldt, Karin, Kommoss, Stefan, Staebler, Annette, Wu, Anna H., Cohen, Paul A., DeFazio, Anna, Lee, Cheng Han, Steed, Helen, Le, Nhu D., Gayther, Simon A., Lawrenson, Kate, Pharoah, Paul D.P., Konecny, Gottfried, Cook, Linda S., Ramus, Susan J., Kelemen, Linda E., and Köbel, Martin
Abstract: Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan–Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81–0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36–0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
Published: 2022

9. Physiotherapy in the prevention and treatment of upper limb complications in women with breast cancer

Author: Pilger, Taynara Louisi, Ortolani, Anna Julia Matheus, Reis, Francisco José Candido dos Reis, Pilger, Taynara Louisi, Ortolani, Anna Julia Matheus, and Reis, Francisco José Candido dos Reis
Abstract: Breast cancer is the one that most affects the female population in Brazil and the world. Upper limb complications are common after cancer treatment, including conservative procedures. Old studies have already shown the effectiveness of physiotherapy in the rehabilitation of these complications. However, currently, physiotherapeutic care must be initiated from the diagnosis of the disease. Pre-rehabilitation prepares the patient to receive cancer treatment and promotes a reduction in rehabilitation time. Rehabilitation decreased the axillary cord by 57%, increased the range of motion (ROM) by 45º for flexion and 70º for shoulder abduction, the incidence of lymphedema was 11%, and there was a decrease of 3.4 points concerning pain on the Visual Scale Analog (EVA). The physical therapist should work with breast cancer to diagnose, prevent, and rehabilitate after cancer treatment, promoting functionality and quality of life for patients with breast cancer., O câncer de mama é o que mais acomete a população feminina no Brasil e no mundo. Complicações do membro superior são comuns após o tratamento oncológico, inclusive em procedimentos conservadores. Estudos antigos já mostravam a eficácia da fisioterapia na reabilitação dessas complicações, contudo, atualmente a atenção fisioterapêutica deve ser iniciada a partir do diagnóstico da doença. A pré-reabilitação prepara a paciente para receber o tratamento oncológico e promove diminuição do tempo de reabilitação. A reabilitação diminuiu o cordão axilar em 57%, aumentou a amplitude de movimento (ADM) em 45º para flexão e 70º para abdução de ombro, a incidência de linfedema é de 11% e há diminuição de 3.4 pontos em relação a dor na Escala Visual Analógica (EVA). O fisioterapeuta deve atuar no câncer de mama no diagnóstico, prevenção e reabilitação pós-tratamento oncológico, promovendo funcionalidade e qualidade de vida para as pacientes com câncer de mama.
Published: 2022

10. Physiotherapy in the prevention and treatment of upper limb complications in women with breast cancer

Author: Pilger, Taynara Louisi, Ortolani, Anna Julia Matheus, Reis, Francisco José Candido dos Reis, Pilger, Taynara Louisi, Ortolani, Anna Julia Matheus, and Reis, Francisco José Candido dos Reis
Abstract: Breast cancer is the one that most affects the female population in Brazil and the world. Upper limb complications are common after cancer treatment, including conservative procedures. Old studies have already shown the effectiveness of physiotherapy in the rehabilitation of these complications. However, currently, physiotherapeutic care must be initiated from the diagnosis of the disease. Pre-rehabilitation prepares the patient to receive cancer treatment and promotes a reduction in rehabilitation time. Rehabilitation decreased the axillary cord by 57%, increased the range of motion (ROM) by 45º for flexion and 70º for shoulder abduction, the incidence of lymphedema was 11%, and there was a decrease of 3.4 points concerning pain on the Visual Scale Analog (EVA). The physical therapist should work with breast cancer to diagnose, prevent, and rehabilitate after cancer treatment, promoting functionality and quality of life for patients with breast cancer., O câncer de mama é o que mais acomete a população feminina no Brasil e no mundo. Complicações do membro superior são comuns após o tratamento oncológico, inclusive em procedimentos conservadores. Estudos antigos já mostravam a eficácia da fisioterapia na reabilitação dessas complicações, contudo, atualmente a atenção fisioterapêutica deve ser iniciada a partir do diagnóstico da doença. A pré-reabilitação prepara a paciente para receber o tratamento oncológico e promove diminuição do tempo de reabilitação. A reabilitação diminuiu o cordão axilar em 57%, aumentou a amplitude de movimento (ADM) em 45º para flexão e 70º para abdução de ombro, a incidência de linfedema é de 11% e há diminuição de 3.4 pontos em relação a dor na Escala Visual Analógica (EVA). O fisioterapeuta deve atuar no câncer de mama no diagnóstico, prevenção e reabilitação pós-tratamento oncológico, promovendo funcionalidade e qualidade de vida para as pacientes com câncer de mama.
Published: 2022

11. Physiotherapy in the prevention and treatment of upper limb complications in women with breast cancer

Author: Pilger, Taynara Louisi, Ortolani, Anna Julia Matheus, Reis, Francisco José Candido dos Reis, Pilger, Taynara Louisi, Ortolani, Anna Julia Matheus, and Reis, Francisco José Candido dos Reis
Abstract: Breast cancer is the one that most affects the female population in Brazil and the world. Upper limb complications are common after cancer treatment, including conservative procedures. Old studies have already shown the effectiveness of physiotherapy in the rehabilitation of these complications. However, currently, physiotherapeutic care must be initiated from the diagnosis of the disease. Pre-rehabilitation prepares the patient to receive cancer treatment and promotes a reduction in rehabilitation time. Rehabilitation decreased the axillary cord by 57%, increased the range of motion (ROM) by 45º for flexion and 70º for shoulder abduction, the incidence of lymphedema was 11%, and there was a decrease of 3.4 points concerning pain on the Visual Scale Analog (EVA). The physical therapist should work with breast cancer to diagnose, prevent, and rehabilitate after cancer treatment, promoting functionality and quality of life for patients with breast cancer., O câncer de mama é o que mais acomete a população feminina no Brasil e no mundo. Complicações do membro superior são comuns após o tratamento oncológico, inclusive em procedimentos conservadores. Estudos antigos já mostravam a eficácia da fisioterapia na reabilitação dessas complicações, contudo, atualmente a atenção fisioterapêutica deve ser iniciada a partir do diagnóstico da doença. A pré-reabilitação prepara a paciente para receber o tratamento oncológico e promove diminuição do tempo de reabilitação. A reabilitação diminuiu o cordão axilar em 57%, aumentou a amplitude de movimento (ADM) em 45º para flexão e 70º para abdução de ombro, a incidência de linfedema é de 11% e há diminuição de 3.4 pontos em relação a dor na Escala Visual Analógica (EVA). O fisioterapeuta deve atuar no câncer de mama no diagnóstico, prevenção e reabilitação pós-tratamento oncológico, promovendo funcionalidade e qualidade de vida para as pacientes com câncer de mama.
Published: 2022

12. Proposal for the development and implementation of a Software for Monitoring Patients with Tuberculosis in Primary Care in the Pandemic: A Critical Analysis

Author: Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, and Ramos, Hugo Vieira
Abstract: Health in Brazil through technological innovations, whether under conditions of equipment availability has been using new techniques of care and care in primary care in diseases communicable with tuberculosis. The aim of this study was to evaluate the national and international scientific production on the knowledge about the process of monitoring tuberculosis patients in Brazilian primary care by software applied by a health professional. The methodology used in this study was the systematic review with a critical analysis in the elaboration for a software and was developed in six stages. As a result, 03 articles were obtained for the construction of this systematic review and the critical analysis in the follow-up of tuberculosis patients in primary care in Brazil. Among the models used, it was noticed that the cascading model, linear or classic and prototyping were the most used for software for care support and educational software.
Published: 2021

13. Proposal for the development and implementation of a Software for Monitoring Patients with Tuberculosis in Primary Care in the Pandemic: A Critical Analysis

Author: Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, and Ramos, Hugo Vieira
Abstract: Health in Brazil through technological innovations, whether under conditions of equipment availability has been using new techniques of care and care in primary care in diseases communicable with tuberculosis. The aim of this study was to evaluate the national and international scientific production on the knowledge about the process of monitoring tuberculosis patients in Brazilian primary care by software applied by a health professional. The methodology used in this study was the systematic review with a critical analysis in the elaboration for a software and was developed in six stages. As a result, 03 articles were obtained for the construction of this systematic review and the critical analysis in the follow-up of tuberculosis patients in primary care in Brazil. Among the models used, it was noticed that the cascading model, linear or classic and prototyping were the most used for software for care support and educational software.
Published: 2021

14. Proposal for the development and implementation of a Software for Monitoring Patients with Tuberculosis in Primary Care in the Pandemic: A Critical Analysis

Author: Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, and Ramos, Hugo Vieira
Abstract: Health in Brazil through technological innovations, whether under conditions of equipment availability has been using new techniques of care and care in primary care in diseases communicable with tuberculosis. The aim of this study was to evaluate the national and international scientific production on the knowledge about the process of monitoring tuberculosis patients in Brazilian primary care by software applied by a health professional. The methodology used in this study was the systematic review with a critical analysis in the elaboration for a software and was developed in six stages. As a result, 03 articles were obtained for the construction of this systematic review and the critical analysis in the follow-up of tuberculosis patients in primary care in Brazil. Among the models used, it was noticed that the cascading model, linear or classic and prototyping were the most used for software for care support and educational software.
Published: 2021

15. Proposal for the development and implementation of a Software for Monitoring Patients with Tuberculosis in Primary Care in the Pandemic: A Critical Analysis

Author: Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, and Ramos, Hugo Vieira
Abstract: Health in Brazil through technological innovations, whether under conditions of equipment availability has been using new techniques of care and care in primary care in diseases communicable with tuberculosis. The aim of this study was to evaluate the national and international scientific production on the knowledge about the process of monitoring tuberculosis patients in Brazilian primary care by software applied by a health professional. The methodology used in this study was the systematic review with a critical analysis in the elaboration for a software and was developed in six stages. As a result, 03 articles were obtained for the construction of this systematic review and the critical analysis in the follow-up of tuberculosis patients in primary care in Brazil. Among the models used, it was noticed that the cascading model, linear or classic and prototyping were the most used for software for care support and educational software.
Published: 2021

16. Proposal for the development and implementation of a Software for Monitoring Patients with Tuberculosis in Primary Care in the Pandemic: A Critical Analysis

Author: Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Ramos, Eliza Miranda, Mendes da Fonseca Junior, Ernani, José Mendes dos Reis, Francisco, Souza, Igor Domingos de, Fonseca, Alessandro Carvalho da, and Ramos, Hugo Vieira
Abstract: Health in Brazil through technological innovations, whether under conditions of equipment availability has been using new techniques of care and care in primary care in diseases communicable with tuberculosis. The aim of this study was to evaluate the national and international scientific production on the knowledge about the process of monitoring tuberculosis patients in Brazilian primary care by software applied by a health professional. The methodology used in this study was the systematic review with a critical analysis in the elaboration for a software and was developed in six stages. As a result, 03 articles were obtained for the construction of this systematic review and the critical analysis in the follow-up of tuberculosis patients in primary care in Brazil. Among the models used, it was noticed that the cascading model, linear or classic and prototyping were the most used for software for care support and educational software.
Published: 2021

17. The Challenge In The Use Of New Technologies Integrated To Health In The Treatment Of Covid-19: A Brief Critical Analysis In Brazil

Author: Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, Ramos, Eliza Miranda, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, and Ramos, Eliza Miranda
Abstract: Viral diseases continue to emerge and annually bring challenges to the Brazilian public health system, such as COVID-19 with easy respiratory infection. This study aims to analyze the importance of new technologies in the treatment of COVID-19 and, thus, promote the information of technological data in the Brazilian territory. Therefore, methodological techniques were used in systematic reviews in the selection of included studies to be used in the construction of this short and critical systematic review. And 08 articles were included for inclusion in this critical analysis.
Published: 2020

18. Vitamin D3 Supplementation: An Option Associated with The Treatment of Multiple Sclerosis: : A Systematic Review and Meta-Analysis

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., and Nascimento, Valter Aragão do
Abstract: Multiple sclerosis (MS) is a chronic complex neurodegenerative disease. A systematic review and meta-analysis were conducted on observational studies and analytics on impact of Vitamin D supplementation in patients with Multiple Sclerosis. In our research, a total of 457 articles were selected and identified for analysis. This systematic review article and meta-analysis, which included evidence from randomized controlled trials conducted with patients with multiple sclerosis, revealed that Vitamin D3 supplementation is effective as an option associated with the treatment of this disease, and that it also has a diffuse protective role against various remission outbreaks in the health. Doses (50,000 IU/week) are appropriate to restore neuroimmunological parameters when used within 12 weeks.
Published: 2020

19. The Use of Vitamin D in The Infectious Process in The Hospital Period in Childhood Effective?

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, and Nascimento, Valter Aragão do
Abstract: Goals: To verify whether the use of Vitamin D as parallel therapy to hospital and drug treatment can be effective in the process of infectious reduction in hospitalized children. Data source: This study is a systematic review and meta-analysis of randomized controlled trials, published between 2011 and the first quarter of 2019, in the Cochrane Library, Medline, US National Library of Medicine and the National Institute of Health (PubMed), Literature databases. Latin American and Caribbean Health Sciences (Lilacs), Scopus and Web of Science. The studies were scored by the Down and Black scale associated with the quality assessment method according to the Cochrane criteria (RCT). Summary of the data: Of the 1475 studies, 09 were included. There is a direct relationship between Vitamin D level and mortality rate in hospitalized children with infections. Conclusion: This study highlighted that the vitamin D deficiency in children under serum analysis during hospitalization triggers severe immunological changes.
Published: 2020

20. Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.

Author: Martins, Filipe Correia, Martins, Filipe Correia, Couturier, Dominique-Laurent, Paterson, Anna, Karnezis, Anthony N, Chow, Christine, Nazeran, Tayyebeh M, Odunsi, Adekunle, Gentry-Maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D, Brooks-Wilson, Angela, DeFazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y, McCauley, Bryan M, Karpinskyj, Chloe, de Sousa, Christiani B, Høgdall, Claus, Tiezzi, Daniel G, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M, Lester, Jenny, Rothstein, Joseph H, de Andrade, Jurandyr M, Lundvall, Lene, Paz-Ares, Luis, Robles-Díaz, Luis, Wilkens, Lynne R, Garcia, Maria J, Intermaggio, Maria P, Alcaraz, Marie-Lyne, Brett, Mary A, Beckmann, Matthias W, Jimenez-Linan, Mercedes, Anglesio, Michael, Carney, Michael E, Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B, Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y, Kaufmann, Scott H, Fereday, Sian, Gayther, Simon, Winham, Stacey J, Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A, McGuire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B, Whittemore, Alice S, Staebler, Annette, Karlan, Beth Y, Rodriguez-Antona, Cristina, Bowtell, David D, Goode, Ellen L, Høgdall, Estrid, Candido Dos Reis, Francisco J, Gronwald, Jacek, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, Fasching, Peter A, Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G, Köbel, Martin, Ramus, Susan J, Pharoah, Paul DP, Brenton, James D, Martins, Filipe Correia, Martins, Filipe Correia, Couturier, Dominique-Laurent, Paterson, Anna, Karnezis, Anthony N, Chow, Christine, Nazeran, Tayyebeh M, Odunsi, Adekunle, Gentry-Maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D, Brooks-Wilson, Angela, DeFazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y, McCauley, Bryan M, Karpinskyj, Chloe, de Sousa, Christiani B, Høgdall, Claus, Tiezzi, Daniel G, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M, Lester, Jenny, Rothstein, Joseph H, de Andrade, Jurandyr M, Lundvall, Lene, Paz-Ares, Luis, Robles-Díaz, Luis, Wilkens, Lynne R, Garcia, Maria J, Intermaggio, Maria P, Alcaraz, Marie-Lyne, Brett, Mary A, Beckmann, Matthias W, Jimenez-Linan, Mercedes, Anglesio, Michael, Carney, Michael E, Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B, Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y, Kaufmann, Scott H, Fereday, Sian, Gayther, Simon, Winham, Stacey J, Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A, McGuire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B, Whittemore, Alice S, Staebler, Annette, Karlan, Beth Y, Rodriguez-Antona, Cristina, Bowtell, David D, Goode, Ellen L, Høgdall, Estrid, Candido Dos Reis, Francisco J, Gronwald, Jacek, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, Fasching, Peter A, Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G, Köbel, Martin, Ramus, Susan J, Pharoah, Paul DP, and Brenton, James D
Abstract: BackgroundPTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.MethodsTumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.ResultsDownregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016).ConclusionsPTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.
Published: 2020

21. The Challenge In The Use Of New Technologies Integrated To Health In The Treatment Of Covid-19: A Brief Critical Analysis In Brazil

Author: Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, Ramos, Eliza Miranda, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, and Ramos, Eliza Miranda
Abstract: Viral diseases continue to emerge and annually bring challenges to the Brazilian public health system, such as COVID-19 with easy respiratory infection. This study aims to analyze the importance of new technologies in the treatment of COVID-19 and, thus, promote the information of technological data in the Brazilian territory. Therefore, methodological techniques were used in systematic reviews in the selection of included studies to be used in the construction of this short and critical systematic review. And 08 articles were included for inclusion in this critical analysis.
Published: 2020

22. Vitamin D3 Supplementation: An Option Associated with The Treatment of Multiple Sclerosis: : A Systematic Review and Meta-Analysis

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., and Nascimento, Valter Aragão do
Abstract: Multiple sclerosis (MS) is a chronic complex neurodegenerative disease. A systematic review and meta-analysis were conducted on observational studies and analytics on impact of Vitamin D supplementation in patients with Multiple Sclerosis. In our research, a total of 457 articles were selected and identified for analysis. This systematic review article and meta-analysis, which included evidence from randomized controlled trials conducted with patients with multiple sclerosis, revealed that Vitamin D3 supplementation is effective as an option associated with the treatment of this disease, and that it also has a diffuse protective role against various remission outbreaks in the health. Doses (50,000 IU/week) are appropriate to restore neuroimmunological parameters when used within 12 weeks.
Published: 2020

23. The Use of Vitamin D in The Infectious Process in The Hospital Period in Childhood Effective?

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, and Nascimento, Valter Aragão do
Abstract: Goals: To verify whether the use of Vitamin D as parallel therapy to hospital and drug treatment can be effective in the process of infectious reduction in hospitalized children. Data source: This study is a systematic review and meta-analysis of randomized controlled trials, published between 2011 and the first quarter of 2019, in the Cochrane Library, Medline, US National Library of Medicine and the National Institute of Health (PubMed), Literature databases. Latin American and Caribbean Health Sciences (Lilacs), Scopus and Web of Science. The studies were scored by the Down and Black scale associated with the quality assessment method according to the Cochrane criteria (RCT). Summary of the data: Of the 1475 studies, 09 were included. There is a direct relationship between Vitamin D level and mortality rate in hospitalized children with infections. Conclusion: This study highlighted that the vitamin D deficiency in children under serum analysis during hospitalization triggers severe immunological changes.
Published: 2020

24. The Use of Vitamin D in The Infectious Process in The Hospital Period in Childhood Effective?

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, and Nascimento, Valter Aragão do
Abstract: Goals: To verify whether the use of Vitamin D as parallel therapy to hospital and drug treatment can be effective in the process of infectious reduction in hospitalized children. Data source: This study is a systematic review and meta-analysis of randomized controlled trials, published between 2011 and the first quarter of 2019, in the Cochrane Library, Medline, US National Library of Medicine and the National Institute of Health (PubMed), Literature databases. Latin American and Caribbean Health Sciences (Lilacs), Scopus and Web of Science. The studies were scored by the Down and Black scale associated with the quality assessment method according to the Cochrane criteria (RCT). Summary of the data: Of the 1475 studies, 09 were included. There is a direct relationship between Vitamin D level and mortality rate in hospitalized children with infections. Conclusion: This study highlighted that the vitamin D deficiency in children under serum analysis during hospitalization triggers severe immunological changes.
Published: 2020

25. The Challenge In The Use Of New Technologies Integrated To Health In The Treatment Of Covid-19: A Brief Critical Analysis In Brazil

Author: Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, Ramos, Eliza Miranda, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, and Ramos, Eliza Miranda
Abstract: Viral diseases continue to emerge and annually bring challenges to the Brazilian public health system, such as COVID-19 with easy respiratory infection. This study aims to analyze the importance of new technologies in the treatment of COVID-19 and, thus, promote the information of technological data in the Brazilian territory. Therefore, methodological techniques were used in systematic reviews in the selection of included studies to be used in the construction of this short and critical systematic review. And 08 articles were included for inclusion in this critical analysis.
Published: 2020

26. Vitamin D3 Supplementation: An Option Associated with The Treatment of Multiple Sclerosis: : A Systematic Review and Meta-Analysis

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., and Nascimento, Valter Aragão do
Abstract: Multiple sclerosis (MS) is a chronic complex neurodegenerative disease. A systematic review and meta-analysis were conducted on observational studies and analytics on impact of Vitamin D supplementation in patients with Multiple Sclerosis. In our research, a total of 457 articles were selected and identified for analysis. This systematic review article and meta-analysis, which included evidence from randomized controlled trials conducted with patients with multiple sclerosis, revealed that Vitamin D3 supplementation is effective as an option associated with the treatment of this disease, and that it also has a diffuse protective role against various remission outbreaks in the health. Doses (50,000 IU/week) are appropriate to restore neuroimmunological parameters when used within 12 weeks.
Published: 2020

27. Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.

Author: Martins, Filipe Correia, Martins, Filipe Correia, Couturier, Dominique-Laurent, Paterson, Anna, Karnezis, Anthony N, Chow, Christine, Nazeran, Tayyebeh M, Odunsi, Adekunle, Gentry-Maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D, Brooks-Wilson, Angela, DeFazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y, McCauley, Bryan M, Karpinskyj, Chloe, de Sousa, Christiani B, Høgdall, Claus, Tiezzi, Daniel G, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M, Lester, Jenny, Rothstein, Joseph H, de Andrade, Jurandyr M, Lundvall, Lene, Paz-Ares, Luis, Robles-Díaz, Luis, Wilkens, Lynne R, Garcia, Maria J, Intermaggio, Maria P, Alcaraz, Marie-Lyne, Brett, Mary A, Beckmann, Matthias W, Jimenez-Linan, Mercedes, Anglesio, Michael, Carney, Michael E, Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B, Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y, Kaufmann, Scott H, Fereday, Sian, Gayther, Simon, Winham, Stacey J, Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A, McGuire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B, Whittemore, Alice S, Staebler, Annette, Karlan, Beth Y, Rodriguez-Antona, Cristina, Bowtell, David D, Goode, Ellen L, Høgdall, Estrid, Candido Dos Reis, Francisco J, Gronwald, Jacek, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, Fasching, Peter A, Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G, Köbel, Martin, Ramus, Susan J, Pharoah, Paul DP, Brenton, James D, Martins, Filipe Correia, Martins, Filipe Correia, Couturier, Dominique-Laurent, Paterson, Anna, Karnezis, Anthony N, Chow, Christine, Nazeran, Tayyebeh M, Odunsi, Adekunle, Gentry-Maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D, Brooks-Wilson, Angela, DeFazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y, McCauley, Bryan M, Karpinskyj, Chloe, de Sousa, Christiani B, Høgdall, Claus, Tiezzi, Daniel G, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M, Lester, Jenny, Rothstein, Joseph H, de Andrade, Jurandyr M, Lundvall, Lene, Paz-Ares, Luis, Robles-Díaz, Luis, Wilkens, Lynne R, Garcia, Maria J, Intermaggio, Maria P, Alcaraz, Marie-Lyne, Brett, Mary A, Beckmann, Matthias W, Jimenez-Linan, Mercedes, Anglesio, Michael, Carney, Michael E, Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B, Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y, Kaufmann, Scott H, Fereday, Sian, Gayther, Simon, Winham, Stacey J, Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A, McGuire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B, Whittemore, Alice S, Staebler, Annette, Karlan, Beth Y, Rodriguez-Antona, Cristina, Bowtell, David D, Goode, Ellen L, Høgdall, Estrid, Candido Dos Reis, Francisco J, Gronwald, Jacek, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, Fasching, Peter A, Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G, Köbel, Martin, Ramus, Susan J, Pharoah, Paul DP, and Brenton, James D
Abstract: BackgroundPTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.MethodsTumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.ResultsDownregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016).ConclusionsPTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.
Published: 2020

28. Vitamin D3 Supplementation: An Option Associated with The Treatment of Multiple Sclerosis: : A Systematic Review and Meta-Analysis

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., and Nascimento, Valter Aragão do
Abstract: Multiple sclerosis (MS) is a chronic complex neurodegenerative disease. A systematic review and meta-analysis were conducted on observational studies and analytics on impact of Vitamin D supplementation in patients with Multiple Sclerosis. In our research, a total of 457 articles were selected and identified for analysis. This systematic review article and meta-analysis, which included evidence from randomized controlled trials conducted with patients with multiple sclerosis, revealed that Vitamin D3 supplementation is effective as an option associated with the treatment of this disease, and that it also has a diffuse protective role against various remission outbreaks in the health. Doses (50,000 IU/week) are appropriate to restore neuroimmunological parameters when used within 12 weeks.
Published: 2020

29. The Use of Vitamin D in The Infectious Process in The Hospital Period in Childhood Effective?

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, and Nascimento, Valter Aragão do
Abstract: Goals: To verify whether the use of Vitamin D as parallel therapy to hospital and drug treatment can be effective in the process of infectious reduction in hospitalized children. Data source: This study is a systematic review and meta-analysis of randomized controlled trials, published between 2011 and the first quarter of 2019, in the Cochrane Library, Medline, US National Library of Medicine and the National Institute of Health (PubMed), Literature databases. Latin American and Caribbean Health Sciences (Lilacs), Scopus and Web of Science. The studies were scored by the Down and Black scale associated with the quality assessment method according to the Cochrane criteria (RCT). Summary of the data: Of the 1475 studies, 09 were included. There is a direct relationship between Vitamin D level and mortality rate in hospitalized children with infections. Conclusion: This study highlighted that the vitamin D deficiency in children under serum analysis during hospitalization triggers severe immunological changes.
Published: 2020

30. The Challenge In The Use Of New Technologies Integrated To Health In The Treatment Of Covid-19: A Brief Critical Analysis In Brazil

Author: Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, Ramos, Eliza Miranda, Fonseca, Alessandro Carvalho da, Ramos, Hugo Vieira, Souza, Igor Domingos de, Reis, Francisco José Mendes dos, and Ramos, Eliza Miranda
Abstract: Viral diseases continue to emerge and annually bring challenges to the Brazilian public health system, such as COVID-19 with easy respiratory infection. This study aims to analyze the importance of new technologies in the treatment of COVID-19 and, thus, promote the information of technological data in the Brazilian territory. Therefore, methodological techniques were used in systematic reviews in the selection of included studies to be used in the construction of this short and critical systematic review. And 08 articles were included for inclusion in this critical analysis.
Published: 2020

31. Vitamin D3 Supplementation: An Option Associated with The Treatment of Multiple Sclerosis: : A Systematic Review and Meta-Analysis

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Reis, Francisco José Mendes dos, Melo, Elaine S. de P., and Nascimento, Valter Aragão do
Abstract: Multiple sclerosis (MS) is a chronic complex neurodegenerative disease. A systematic review and meta-analysis were conducted on observational studies and analytics on impact of Vitamin D supplementation in patients with Multiple Sclerosis. In our research, a total of 457 articles were selected and identified for analysis. This systematic review article and meta-analysis, which included evidence from randomized controlled trials conducted with patients with multiple sclerosis, revealed that Vitamin D3 supplementation is effective as an option associated with the treatment of this disease, and that it also has a diffuse protective role against various remission outbreaks in the health. Doses (50,000 IU/week) are appropriate to restore neuroimmunological parameters when used within 12 weeks.
Published: 2020

32. The Use of Vitamin D in The Infectious Process in The Hospital Period in Childhood Effective?

Author: Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, Nascimento, Valter Aragão do, Ramos, Eliza Miranda, Lima, Matheus Dullius de, Gonzalez, Jéssica Eloy Cunha, Facco, Gilberto Gonçalves, Melo, Elaine S. de P., Ramos, Hugo Vieira, Reis, Francisco José Mendes dos, Souza, Igor Domingos de, and Nascimento, Valter Aragão do
Abstract: Goals: To verify whether the use of Vitamin D as parallel therapy to hospital and drug treatment can be effective in the process of infectious reduction in hospitalized children. Data source: This study is a systematic review and meta-analysis of randomized controlled trials, published between 2011 and the first quarter of 2019, in the Cochrane Library, Medline, US National Library of Medicine and the National Institute of Health (PubMed), Literature databases. Latin American and Caribbean Health Sciences (Lilacs), Scopus and Web of Science. The studies were scored by the Down and Black scale associated with the quality assessment method according to the Cochrane criteria (RCT). Summary of the data: Of the 1475 studies, 09 were included. There is a direct relationship between Vitamin D level and mortality rate in hospitalized children with infections. Conclusion: This study highlighted that the vitamin D deficiency in children under serum analysis during hospitalization triggers severe immunological changes.
Published: 2020

33. Clinical and pathological associations of PTEN expression in ovarian cancer:a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Author: Martins, Filipe Correia, Couturier, Dominique-laurent, Paterson, Anna, Karnezis, Anthony N., Chow, Christine, Nazeran, Tayyebeh M., Odunsi, Adekunle, Gentry-maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D., Brooks-wilson, Angela, Defazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y., Mccauley, Bryan M., Karpinskyj, Chloe, De Sousa, Christiani B., Høgdall, Claus, Tiezzi, Daniel G., Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M., Lester, Jenny, Rothstein, Joseph H., De Andrade, Jurandyr M., Lundvall, Lene, Paz-ares, Luis, Robles-díaz, Luis, Wilkens, Lynne R., Garcia, Maria J., Intermaggio, Maria P., Alcaraz, Marie-lyne, Brett, Mary A., Beckmann, Matthias W., Jimenez-linan, Mercedes, Anglesio, Michael, Carney, Michael E., Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B., Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y., Kaufmann, Scott H., Fereday, Sian, Gayther, Simon, Winham, Stacey J., Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A., Mcguire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B., Whittemore, Alice S., Staebler, Annette, Karlan, Beth Y., Rodriguez-antona, Cristina, Bowtell, David D., Goode, Ellen L., Høgdall, Estrid, Candido Dos Reis, Francisco J., Gronwald, Jacek, Chang-claude, Jenny, Moysich, Kirsten B., Kelemen, Linda E., Cook, Linda S., Goodman, Marc T., Fasching, Peter A., Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G., Köbel, Martin, Ramus, Susan J., Pharoah, Paul D. P., Brenton, James D., Martins, Filipe Correia, Couturier, Dominique-laurent, Paterson, Anna, Karnezis, Anthony N., Chow, Christine, Nazeran, Tayyebeh M., Odunsi, Adekunle, Gentry-maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D., Brooks-wilson, Angela, Defazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y., Mccauley, Bryan M., Karpinskyj, Chloe, De Sousa, Christiani B., Høgdall, Claus, Tiezzi, Daniel G., Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M., Lester, Jenny, Rothstein, Joseph H., De Andrade, Jurandyr M., Lundvall, Lene, Paz-ares, Luis, Robles-díaz, Luis, Wilkens, Lynne R., Garcia, Maria J., Intermaggio, Maria P., Alcaraz, Marie-lyne, Brett, Mary A., Beckmann, Matthias W., Jimenez-linan, Mercedes, Anglesio, Michael, Carney, Michael E., Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B., Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y., Kaufmann, Scott H., Fereday, Sian, Gayther, Simon, Winham, Stacey J., Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A., Mcguire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B., Whittemore, Alice S., Staebler, Annette, Karlan, Beth Y., Rodriguez-antona, Cristina, Bowtell, David D., Goode, Ellen L., Høgdall, Estrid, Candido Dos Reis, Francisco J., Gronwald, Jacek, Chang-claude, Jenny, Moysich, Kirsten B., Kelemen, Linda E., Cook, Linda S., Goodman, Marc T., Fasching, Peter A., Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G., Köbel, Martin, Ramus, Susan J., Pharoah, Paul D. P., and Brenton, James D.
Published: 2020

34. Clinical and pathological associations of PTEN expression in ovarian cancer:a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Author: Martins, Filipe Correia, Couturier, Dominique-laurent, Paterson, Anna, Karnezis, Anthony N., Chow, Christine, Nazeran, Tayyebeh M., Odunsi, Adekunle, Gentry-maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D., Brooks-wilson, Angela, Defazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y., Mccauley, Bryan M., Karpinskyj, Chloe, De Sousa, Christiani B., Høgdall, Claus, Tiezzi, Daniel G., Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M., Lester, Jenny, Rothstein, Joseph H., De Andrade, Jurandyr M., Lundvall, Lene, Paz-ares, Luis, Robles-díaz, Luis, Wilkens, Lynne R., Garcia, Maria J., Intermaggio, Maria P., Alcaraz, Marie-lyne, Brett, Mary A., Beckmann, Matthias W., Jimenez-linan, Mercedes, Anglesio, Michael, Carney, Michael E., Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B., Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y., Kaufmann, Scott H., Fereday, Sian, Gayther, Simon, Winham, Stacey J., Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A., Mcguire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B., Whittemore, Alice S., Staebler, Annette, Karlan, Beth Y., Rodriguez-antona, Cristina, Bowtell, David D., Goode, Ellen L., Høgdall, Estrid, Candido Dos Reis, Francisco J., Gronwald, Jacek, Chang-claude, Jenny, Moysich, Kirsten B., Kelemen, Linda E., Cook, Linda S., Goodman, Marc T., Fasching, Peter A., Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G., Köbel, Martin, Ramus, Susan J., Pharoah, Paul D. P., Brenton, James D., Martins, Filipe Correia, Couturier, Dominique-laurent, Paterson, Anna, Karnezis, Anthony N., Chow, Christine, Nazeran, Tayyebeh M., Odunsi, Adekunle, Gentry-maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D., Brooks-wilson, Angela, Defazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y., Mccauley, Bryan M., Karpinskyj, Chloe, De Sousa, Christiani B., Høgdall, Claus, Tiezzi, Daniel G., Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M., Lester, Jenny, Rothstein, Joseph H., De Andrade, Jurandyr M., Lundvall, Lene, Paz-ares, Luis, Robles-díaz, Luis, Wilkens, Lynne R., Garcia, Maria J., Intermaggio, Maria P., Alcaraz, Marie-lyne, Brett, Mary A., Beckmann, Matthias W., Jimenez-linan, Mercedes, Anglesio, Michael, Carney, Michael E., Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B., Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y., Kaufmann, Scott H., Fereday, Sian, Gayther, Simon, Winham, Stacey J., Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A., Mcguire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B., Whittemore, Alice S., Staebler, Annette, Karlan, Beth Y., Rodriguez-antona, Cristina, Bowtell, David D., Goode, Ellen L., Høgdall, Estrid, Candido Dos Reis, Francisco J., Gronwald, Jacek, Chang-claude, Jenny, Moysich, Kirsten B., Kelemen, Linda E., Cook, Linda S., Goodman, Marc T., Fasching, Peter A., Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G., Köbel, Martin, Ramus, Susan J., Pharoah, Paul D. P., and Brenton, James D.
Published: 2020

35. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer.

Author: Candido-dos-Reis, Francisco J, Candido-dos-Reis, Francisco J, Song, Honglin, Goode, Ellen L, Cunningham, Julie M, Fridley, Brooke L, Larson, Melissa C, Alsop, Kathryn, Dicks, Ed, Harrington, Patricia, Ramus, Susan J, de Fazio, Anna, Mitchell, Gillian, Fereday, Sian, Bolton, Kelly L, Gourley, Charlie, Michie, Caroline, Karlan, Beth, Lester, Jenny, Walsh, Christine, Cass, Ilana, Olsson, Håkan, Gore, Martin, Benitez, Javier J, Garcia, Maria J, Andrulis, Irene, Mulligan, Anna Marie, Glendon, Gord, Blanco, Ignacio, Lazaro, Conxi, Whittemore, Alice S, McGuire, Valerie, Sieh, Weiva, Montagna, Marco, Alducci, Elisa, Sadetzki, Siegal, Chetrit, Angela, Kwong, Ava, Kjaer, Susanne K, Jensen, Allan, Høgdall, Estrid, Neuhausen, Susan, Nussbaum, Robert, Daly, Mary, Greene, Mark H, Mai, Phuong L, Loud, Jennifer T, Moysich, Kirsten, Toland, Amanda E, Lambrechts, Diether, Ellis, Steve, Frost, Debra, Brenton, James D, Tischkowitz, Marc, Easton, Douglas F, Antoniou, Antonis, Chenevix-Trench, Georgia, Gayther, Simon A, Bowtell, David, Pharoah, Paul DP, for EMBRACE, kConFab Investigators, Australian Ovarian Cancer Study Group, Candido-dos-Reis, Francisco J, Candido-dos-Reis, Francisco J, Song, Honglin, Goode, Ellen L, Cunningham, Julie M, Fridley, Brooke L, Larson, Melissa C, Alsop, Kathryn, Dicks, Ed, Harrington, Patricia, Ramus, Susan J, de Fazio, Anna, Mitchell, Gillian, Fereday, Sian, Bolton, Kelly L, Gourley, Charlie, Michie, Caroline, Karlan, Beth, Lester, Jenny, Walsh, Christine, Cass, Ilana, Olsson, Håkan, Gore, Martin, Benitez, Javier J, Garcia, Maria J, Andrulis, Irene, Mulligan, Anna Marie, Glendon, Gord, Blanco, Ignacio, Lazaro, Conxi, Whittemore, Alice S, McGuire, Valerie, Sieh, Weiva, Montagna, Marco, Alducci, Elisa, Sadetzki, Siegal, Chetrit, Angela, Kwong, Ava, Kjaer, Susanne K, Jensen, Allan, Høgdall, Estrid, Neuhausen, Susan, Nussbaum, Robert, Daly, Mary, Greene, Mark H, Mai, Phuong L, Loud, Jennifer T, Moysich, Kirsten, Toland, Amanda E, Lambrechts, Diether, Ellis, Steve, Frost, Debra, Brenton, James D, Tischkowitz, Marc, Easton, Douglas F, Antoniou, Antonis, Chenevix-Trench, Georgia, Gayther, Simon A, Bowtell, David, Pharoah, Paul DP, for EMBRACE, kConFab Investigators, and Australian Ovarian Cancer Study Group
Abstract: PurposeTo analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.Experimental designWe used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.ResultsThe combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.ConclusionsBRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
Published: 2015

36. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.

Author: Rambau, Peter F, Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, de Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, de Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, AOCS Group, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, Köbel, Martin, Rambau, Peter F, Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, de Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, de Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, AOCS Group, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, and Köbel, Martin
Abstract: We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.
Published: 2018

37. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

Author: Block, Matthew S, Block, Matthew S, Vierkant, Robert A, Rambau, Peter F, Winham, Stacey J, Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G, Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H, Ramón Y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B, Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M, Mack, Marie, Lubiński, Jan, Longacre, Teri A, Li, Zheng, Lester, Jenny, Kennedy, Catherine J, Kalli, Kimberly R, Jung, Audrey Y, Johnatty, Sharon E, Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P, Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y, Hartkopf, Andreas D, Harnett, Paul R, Ghatage, Prafull, García-Bueno, José M, Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P, de Sousa, Christiani B, de Andrade, Jurandyr M, Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y, Australian Ovarian Cancer Study Group, Alsop, Jennifer, Whittemore, Alice S, Steed, Helen, Staebler, Annette, Moysich, Kirsten B, Menon, Usha, Koziak, Jennifer M, Kommoss, Stefan, Kjaer, Susanne K, Kelemen, Linda E, Karlan, Beth Y, Huntsman, David G, Høgdall, Estrid, Gronwald, Jacek, Goodman, Marc T, Gilks, Blake, García, María José, Fasching, Peter A, de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido Dos Reis, Francisco J, Campbell, Ian G, Brenton, James D, Bowtell, David D, Benítez, Javier, Pharoah, Paul DP, Köbel, Martin, Ramus, Susan J, Goode, Ellen L, Block, Matthew S, Block, Matthew S, Vierkant, Robert A, Rambau, Peter F, Winham, Stacey J, Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G, Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H, Ramón Y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B, Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M, Mack, Marie, Lubiński, Jan, Longacre, Teri A, Li, Zheng, Lester, Jenny, Kennedy, Catherine J, Kalli, Kimberly R, Jung, Audrey Y, Johnatty, Sharon E, Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P, Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y, Hartkopf, Andreas D, Harnett, Paul R, Ghatage, Prafull, García-Bueno, José M, Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P, de Sousa, Christiani B, de Andrade, Jurandyr M, Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y, Australian Ovarian Cancer Study Group, Alsop, Jennifer, Whittemore, Alice S, Steed, Helen, Staebler, Annette, Moysich, Kirsten B, Menon, Usha, Koziak, Jennifer M, Kommoss, Stefan, Kjaer, Susanne K, Kelemen, Linda E, Karlan, Beth Y, Huntsman, David G, Høgdall, Estrid, Gronwald, Jacek, Goodman, Marc T, Gilks, Blake, García, María José, Fasching, Peter A, de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido Dos Reis, Francisco J, Campbell, Ian G, Brenton, James D, Bowtell, David D, Benítez, Javier, Pharoah, Paul DP, Köbel, Martin, Ramus, Susan J, and Goode, Ellen L
Abstract: ObjectiveTo evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.Patients and methodsWe conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).ResultsExpression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively).ConclusionResults are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.
Published: 2018

38. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

Author: Block, Matthew S, Block, Matthew S, Vierkant, Robert A, Rambau, Peter F, Winham, Stacey J, Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G, Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H, Ramón Y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B, Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M, Mack, Marie, Lubiński, Jan, Longacre, Teri A, Li, Zheng, Lester, Jenny, Kennedy, Catherine J, Kalli, Kimberly R, Jung, Audrey Y, Johnatty, Sharon E, Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P, Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y, Hartkopf, Andreas D, Harnett, Paul R, Ghatage, Prafull, García-Bueno, José M, Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P, de Sousa, Christiani B, de Andrade, Jurandyr M, Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y, Australian Ovarian Cancer Study Group, Alsop, Jennifer, Whittemore, Alice S, Steed, Helen, Staebler, Annette, Moysich, Kirsten B, Menon, Usha, Koziak, Jennifer M, Kommoss, Stefan, Kjaer, Susanne K, Kelemen, Linda E, Karlan, Beth Y, Huntsman, David G, Høgdall, Estrid, Gronwald, Jacek, Goodman, Marc T, Gilks, Blake, García, María José, Fasching, Peter A, de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido Dos Reis, Francisco J, Campbell, Ian G, Brenton, James D, Bowtell, David D, Benítez, Javier, Pharoah, Paul DP, Köbel, Martin, Ramus, Susan J, Goode, Ellen L, Block, Matthew S, Block, Matthew S, Vierkant, Robert A, Rambau, Peter F, Winham, Stacey J, Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G, Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H, Ramón Y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B, Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M, Mack, Marie, Lubiński, Jan, Longacre, Teri A, Li, Zheng, Lester, Jenny, Kennedy, Catherine J, Kalli, Kimberly R, Jung, Audrey Y, Johnatty, Sharon E, Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P, Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y, Hartkopf, Andreas D, Harnett, Paul R, Ghatage, Prafull, García-Bueno, José M, Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P, de Sousa, Christiani B, de Andrade, Jurandyr M, Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y, Australian Ovarian Cancer Study Group, Alsop, Jennifer, Whittemore, Alice S, Steed, Helen, Staebler, Annette, Moysich, Kirsten B, Menon, Usha, Koziak, Jennifer M, Kommoss, Stefan, Kjaer, Susanne K, Kelemen, Linda E, Karlan, Beth Y, Huntsman, David G, Høgdall, Estrid, Gronwald, Jacek, Goodman, Marc T, Gilks, Blake, García, María José, Fasching, Peter A, de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido Dos Reis, Francisco J, Campbell, Ian G, Brenton, James D, Bowtell, David D, Benítez, Javier, Pharoah, Paul DP, Köbel, Martin, Ramus, Susan J, and Goode, Ellen L
Abstract: ObjectiveTo evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.Patients and methodsWe conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).ResultsExpression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively).ConclusionResults are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.
Published: 2018

39. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.

Author: Rambau, Peter F, Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, de Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, de Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, AOCS Group, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, Köbel, Martin, Rambau, Peter F, Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, de Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, de Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, AOCS Group, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, and Köbel, Martin
Abstract: We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.
Published: 2018

40. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes:an Ovarian Tumor Tissue Analysis consortium study

Author: Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, De Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, De Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, Köbel, Martin, Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, De Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, De Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, and Köbel, Martin
Published: 2018

41. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes:an Ovarian Tumor Tissue Analysis consortium study

Author: Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, De Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, De Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, Köbel, Martin, Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, De Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, De Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, and Köbel, Martin
Published: 2018

42. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

Author: Ovarian Tumor Tissue Analysis (OTTA) Consortium, Ovarian Tumor Tissue Analysis (OTTA) Consortium, Goode, Ellen L, Block, Matthew S, Kalli, Kimberly R, Vierkant, Robert A, Chen, Wenqian, Fogarty, Zachary C, Gentry-Maharaj, Aleksandra, Tołoczko, Aleksandra, Hein, Alexander, Bouligny, Aliecia L, Jensen, Allan, Osorio, Ana, Hartkopf, Andreas, Ryan, Andy, Chudecka-Głaz, Anita, Magliocco, Anthony M, Hartmann, Arndt, Jung, Audrey Y, Gao, Bo, Hernandez, Brenda Y, Fridley, Brooke L, McCauley, Bryan M, Kennedy, Catherine J, Wang, Chen, Karpinskyj, Chloe, de Sousa, Christiani B, Tiezzi, Daniel G, Wachter, David L, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Nelson, Gregg, Lubiński, Jan, Menkiszak, Janusz, Alsop, Jennifer, Lester, Jenny, García-Donas, Jesús, Nation, Jill, Hung, Jillian, Palacios, José, Rothstein, Joseph H, Kelley, Joseph L, de Andrade, Jurandyr M, Robles-Díaz, Luis, Intermaggio, Maria P, Widschwendter, Martin, Beckmann, Matthias W, Ruebner, Matthias, Jimenez-Linan, Mercedes, Singh, Naveena, Oszurek, Oleg, Harnett, Paul R, Rambau, Peter F, Sinn, Peter, Wagner, Philipp, Ghatage, Prafull, Sharma, Raghwa, Edwards, Robert P, Ness, Roberta B, Orsulic, Sandra, Brucker, Sara Y, Johnatty, Sharon E, Longacre, Teri A, Ursula, Eilber, McGuire, Valerie, Sieh, Weiva, Natanzon, Yanina, Li, Zheng, Whittemore, Alice S, Anna, deFazio, Staebler, Annette, Karlan, Beth Y, Gilks, Blake, Bowtell, David D, Høgdall, Estrid, Candido dos Reis, Francisco J, Steed, Helen, Campbell, Ian G, Gronwald, Jacek, Benítez, Javier, Koziak, Jennifer M, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, García, María José, Fasching, Peter A, Kommoss, Stefan, Deen, Suha, Kjaer, Susanne K, Menon, Usha, Brenton, James D, Pharoah, Paul DP, Chenevix-Trench, Georgia, Huntsman, David G, Winham, Stacey J, Köbel, Martin, Ramus, Susan J, Ovarian Tumor Tissue Analysis (OTTA) Consortium, Ovarian Tumor Tissue Analysis (OTTA) Consortium, Goode, Ellen L, Block, Matthew S, Kalli, Kimberly R, Vierkant, Robert A, Chen, Wenqian, Fogarty, Zachary C, Gentry-Maharaj, Aleksandra, Tołoczko, Aleksandra, Hein, Alexander, Bouligny, Aliecia L, Jensen, Allan, Osorio, Ana, Hartkopf, Andreas, Ryan, Andy, Chudecka-Głaz, Anita, Magliocco, Anthony M, Hartmann, Arndt, Jung, Audrey Y, Gao, Bo, Hernandez, Brenda Y, Fridley, Brooke L, McCauley, Bryan M, Kennedy, Catherine J, Wang, Chen, Karpinskyj, Chloe, de Sousa, Christiani B, Tiezzi, Daniel G, Wachter, David L, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Nelson, Gregg, Lubiński, Jan, Menkiszak, Janusz, Alsop, Jennifer, Lester, Jenny, García-Donas, Jesús, Nation, Jill, Hung, Jillian, Palacios, José, Rothstein, Joseph H, Kelley, Joseph L, de Andrade, Jurandyr M, Robles-Díaz, Luis, Intermaggio, Maria P, Widschwendter, Martin, Beckmann, Matthias W, Ruebner, Matthias, Jimenez-Linan, Mercedes, Singh, Naveena, Oszurek, Oleg, Harnett, Paul R, Rambau, Peter F, Sinn, Peter, Wagner, Philipp, Ghatage, Prafull, Sharma, Raghwa, Edwards, Robert P, Ness, Roberta B, Orsulic, Sandra, Brucker, Sara Y, Johnatty, Sharon E, Longacre, Teri A, Ursula, Eilber, McGuire, Valerie, Sieh, Weiva, Natanzon, Yanina, Li, Zheng, Whittemore, Alice S, Anna, deFazio, Staebler, Annette, Karlan, Beth Y, Gilks, Blake, Bowtell, David D, Høgdall, Estrid, Candido dos Reis, Francisco J, Steed, Helen, Campbell, Ian G, Gronwald, Jacek, Benítez, Javier, Koziak, Jennifer M, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, García, María José, Fasching, Peter A, Kommoss, Stefan, Deen, Suha, Kjaer, Susanne K, Menon, Usha, Brenton, James D, Pharoah, Paul DP, Chenevix-Trench, Georgia, Huntsman, David G, Winham, Stacey J, Köbel, Martin, and Ramus, Susan J
Abstract: ImportanceCytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.ObjectiveTo define the prognostic role of CD8+ TILs in epithelial ovarian cancer.Design, setting, and participantsThis was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.ExposuresFollowing immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.Main outcomes and measuresOverall survival time.ResultsThe final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+
Published: 2017

43. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

Author: Ovarian Tumor Tissue Analysis (OTTA) Consortium, Ovarian Tumor Tissue Analysis (OTTA) Consortium, Goode, Ellen L, Block, Matthew S, Kalli, Kimberly R, Vierkant, Robert A, Chen, Wenqian, Fogarty, Zachary C, Gentry-Maharaj, Aleksandra, Tołoczko, Aleksandra, Hein, Alexander, Bouligny, Aliecia L, Jensen, Allan, Osorio, Ana, Hartkopf, Andreas, Ryan, Andy, Chudecka-Głaz, Anita, Magliocco, Anthony M, Hartmann, Arndt, Jung, Audrey Y, Gao, Bo, Hernandez, Brenda Y, Fridley, Brooke L, McCauley, Bryan M, Kennedy, Catherine J, Wang, Chen, Karpinskyj, Chloe, de Sousa, Christiani B, Tiezzi, Daniel G, Wachter, David L, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Nelson, Gregg, Lubiński, Jan, Menkiszak, Janusz, Alsop, Jennifer, Lester, Jenny, García-Donas, Jesús, Nation, Jill, Hung, Jillian, Palacios, José, Rothstein, Joseph H, Kelley, Joseph L, de Andrade, Jurandyr M, Robles-Díaz, Luis, Intermaggio, Maria P, Widschwendter, Martin, Beckmann, Matthias W, Ruebner, Matthias, Jimenez-Linan, Mercedes, Singh, Naveena, Oszurek, Oleg, Harnett, Paul R, Rambau, Peter F, Sinn, Peter, Wagner, Philipp, Ghatage, Prafull, Sharma, Raghwa, Edwards, Robert P, Ness, Roberta B, Orsulic, Sandra, Brucker, Sara Y, Johnatty, Sharon E, Longacre, Teri A, Ursula, Eilber, McGuire, Valerie, Sieh, Weiva, Natanzon, Yanina, Li, Zheng, Whittemore, Alice S, Anna, deFazio, Staebler, Annette, Karlan, Beth Y, Gilks, Blake, Bowtell, David D, Høgdall, Estrid, Candido dos Reis, Francisco J, Steed, Helen, Campbell, Ian G, Gronwald, Jacek, Benítez, Javier, Koziak, Jennifer M, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, García, María José, Fasching, Peter A, Kommoss, Stefan, Deen, Suha, Kjaer, Susanne K, Menon, Usha, Brenton, James D, Pharoah, Paul DP, Chenevix-Trench, Georgia, Huntsman, David G, Winham, Stacey J, Köbel, Martin, Ramus, Susan J, Ovarian Tumor Tissue Analysis (OTTA) Consortium, Ovarian Tumor Tissue Analysis (OTTA) Consortium, Goode, Ellen L, Block, Matthew S, Kalli, Kimberly R, Vierkant, Robert A, Chen, Wenqian, Fogarty, Zachary C, Gentry-Maharaj, Aleksandra, Tołoczko, Aleksandra, Hein, Alexander, Bouligny, Aliecia L, Jensen, Allan, Osorio, Ana, Hartkopf, Andreas, Ryan, Andy, Chudecka-Głaz, Anita, Magliocco, Anthony M, Hartmann, Arndt, Jung, Audrey Y, Gao, Bo, Hernandez, Brenda Y, Fridley, Brooke L, McCauley, Bryan M, Kennedy, Catherine J, Wang, Chen, Karpinskyj, Chloe, de Sousa, Christiani B, Tiezzi, Daniel G, Wachter, David L, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Nelson, Gregg, Lubiński, Jan, Menkiszak, Janusz, Alsop, Jennifer, Lester, Jenny, García-Donas, Jesús, Nation, Jill, Hung, Jillian, Palacios, José, Rothstein, Joseph H, Kelley, Joseph L, de Andrade, Jurandyr M, Robles-Díaz, Luis, Intermaggio, Maria P, Widschwendter, Martin, Beckmann, Matthias W, Ruebner, Matthias, Jimenez-Linan, Mercedes, Singh, Naveena, Oszurek, Oleg, Harnett, Paul R, Rambau, Peter F, Sinn, Peter, Wagner, Philipp, Ghatage, Prafull, Sharma, Raghwa, Edwards, Robert P, Ness, Roberta B, Orsulic, Sandra, Brucker, Sara Y, Johnatty, Sharon E, Longacre, Teri A, Ursula, Eilber, McGuire, Valerie, Sieh, Weiva, Natanzon, Yanina, Li, Zheng, Whittemore, Alice S, Anna, deFazio, Staebler, Annette, Karlan, Beth Y, Gilks, Blake, Bowtell, David D, Høgdall, Estrid, Candido dos Reis, Francisco J, Steed, Helen, Campbell, Ian G, Gronwald, Jacek, Benítez, Javier, Koziak, Jennifer M, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, García, María José, Fasching, Peter A, Kommoss, Stefan, Deen, Suha, Kjaer, Susanne K, Menon, Usha, Brenton, James D, Pharoah, Paul DP, Chenevix-Trench, Georgia, Huntsman, David G, Winham, Stacey J, Köbel, Martin, and Ramus, Susan J
Abstract: ImportanceCytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.ObjectiveTo define the prognostic role of CD8+ TILs in epithelial ovarian cancer.Design, setting, and participantsThis was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.ExposuresFollowing immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.Main outcomes and measuresOverall survival time.ResultsThe final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+
Published: 2017

44. Tecnologias desenvolvidas pelas instituições de ensino superior para idosos com deficiência

Author: Prestes de Godoi, Hundra, Balbinot Reis Girondi, Juliana, Lusia Ropelato Fernandez, Darla, Reis, Francisco, Oliveira Pires, Fernanda Rosa, Schier, Jordelina, Prestes de Godoi, Hundra, Balbinot Reis Girondi, Juliana, Lusia Ropelato Fernandez, Darla, Reis, Francisco, Oliveira Pires, Fernanda Rosa, and Schier, Jordelina
Abstract: Introduction: Older people with disabilities are gradually prevalent, with increasing population aging and chronic diseases,. Accordingly, health education institutions should prepare future professionals for these demands by developing learning opportunities and new technologies of care. Objective: to investigate the technologies of elderly care with disabilities in Higher Education Institutions that offer courses in health care in the region of “Florianópolis / SC”. Methodology: a mixed exploratory-descriptive research carried out with 26 coordinators of IES courses in “Grande Florianópolis” / from November / 2016 to April / 2017. Data were collected through a structured questionnaire and submitted to Minayo content thematic analysis. The results were discussed through relevant literature. Results: 86% of the courses offered are for the elderly and 59% for the elderly with disabilities. As for the research and extension projects, 72.7% of the courses carry out projects for the elderly and 50% specifically for the elderly with disabilities. In terms of leisure activities, 23% of the coordinators answered that they are doing it for the elderly and 18% for the elderly with disabilities. Conclusions: most of the undergraduate courses in the health area develop care technologies related to aging and disabilities, but relate them to the curriculum, research and extension are still incipient, considering the emerging population problem in Brazil., Introdução: Com o aumento do envelhecimento populacional e das Doenças Crônicas é cada vez mais prevalente pessoas idosas com deficiência. Consoante, as instituições formadoras na área da saúde devem preparar os futuros profissionais para estas demandas desenvolvendo oportunidades de aprendizado e novas tecnologias de cuidado. Objetivo: investigar as tecnologias de cuidado ao idoso com deficiência nas Instituições de Ensino Superior (IES) que oferecem cursos na área da saúde na região da Grande Florianópolis/Santa Catarina. Método: pesquisa mista exploratório-descritiva realizada com 26 coordenadores de cursos de saúde das IES da Grande Florianópolis/ de novembro/2016 a abril/2017. Os dados foram coletados mediante questionário estruturado e submetidos à análise temática de conteúdo de Minayo. Os resultados foram discutidos à luz da literatura pertinente. Resultados: dos atendimentos realizados, 86% dos cursos o desenvolvem somente para idosos e 59% para idoso com deficiência. Quanto aos projetos de pesquisa e extensão 72,7% dos cursos realizam projetos para pessoas idosas e 50% especificamente para idosos com deficiência. No quesito atividades de lazer, 23% dos coordenadores responderam que as realizam para o público idoso e 18% ao idoso com deficiência. Conclusões: a maioria dos cursos de graduação na área da saúde desenvolve tecnologias de cuidado relacionadas ao envelhecimento e deficiências, mas relacioná-los ao currículo, pesquisa e extensão ainda são incipientes, considerando a problemática populacional emergente no Brasil., Introducción: Con el crecimiento del envejecimiento poblacional y de las enfermedades crónicas es cada vez más común que hayan personas mayores con discapacidad. Además, las universidades y escuelas que tienen cursos en el área de la salud deben preparar a los futuros profesionales para estas demandas desarrollando oportunidades de aprendizaje y nuevas tecnologías de cuidado. Objetivo: investigar las tecnologías de cuidado al anciano con discapacidad en las Instituciones de enseñanza superior (IES) que ofrecen cursos en el área de la salud en la región de la Grande Florianópolis / SC. Metodología: investigación mixta exploratoria-descriptiva realizada con 26 coordinadores de cursos de salud de las IES de la Grande Florianópolis / de noviembre / 2016 a abril / 2017. Los datos fueron recolectados mediante cuestionario estructurado y sometidos al análisis temático de contenido de Minayo. Los resultados se discutieron con base en la literatura relacionada. Resultados: de las atenciones realizadas 86% de los cursos lo desarrollan solamente para ancianos y 59% para ancianos con discapacidad. Los proyectos de investigación y extensión el 72,7% de los cursos realizan proyectos para personas mayores y 50% específicamente para ancianos con discapacidad. En relacion a las actividades de ocio el 23% de los coordinadores respondieron que las realizan para el público anciano y el 18% al anciano con discapacidad. Conclusiones: la mayoría de los cursos de graduación en el área de la salud desarrollan tecnologías de cuidado relacionadas con el envejecimiento y deficiencias, pero relacionarlos al currículo, investigación y extensión todavía son insuficientes, considerando la problemática poblacional emergente en Brasil.
Published: 2017

45. Effects of climate change on the distribution of indigenous species in oceanic islands (Azores)

Author: Ferreira, Maria Teresa, Cardoso, Pedro, Borges, Paulo A. V., Gabriel, Rosalina, de Azevedo, Eduardo Brito, Reis, Francisco, Bastos, Miguel, Elias, Rui Bento, Ferreira, Maria Teresa, Cardoso, Pedro, Borges, Paulo A. V., Gabriel, Rosalina, de Azevedo, Eduardo Brito, Reis, Francisco, Bastos, Miguel, and Elias, Rui Bento
Published: 2016

46. Effects of climate change on the distribution of indigenous species in oceanic islands (Azores)

Author: Azorean Regional Fund for Science and Technology, European Commission, Ferreira, Maria Teresa, Cardoso, Pedro, Borges, Paulo A.V., Gabriel, Rosalina, Brito de Azevedo, Eduardo, Reis, Francisco, Araújo, Miguel B., Bento Elías, Rui, Azorean Regional Fund for Science and Technology, European Commission, Ferreira, Maria Teresa, Cardoso, Pedro, Borges, Paulo A.V., Gabriel, Rosalina, Brito de Azevedo, Eduardo, Reis, Francisco, Araújo, Miguel B., and Bento Elías, Rui
Abstract: Oceanic islands host a high proportion of the world’s endemic species. Many such species are at risk of extinction owing to habitat degradation and loss, biological invasions and other threats, but little is known about the effects of climate change on island native biodiversity. The Azorean archipelago provides a unique opportunity to study species-climate-change relationships. We used ensemble forecasting to evaluate the current and future distribution of well-studied endemic and native bryophytes (19 species), endemic vascular plants (59 species) and endemic arthropods (128 species), for two of the largest Azorean Islands, Terceira and São Miguel. Using a Regional Climate Model (CIELO), and assuming the extreme scenario RCP8.5, we examined changes in the potential distributions of the species and possible loss of climate space for them. Models projected that 23 species (11 %) could lose all adequate climate on either one or both islands. Five additional species were projected to lose ≥90 % of climate space. In total, 90 % of the species were projected to lose climate space: 79 % of bryophytes, 93 % of vascular plants and 91 % of arthropods. We also found for vascular plants and arthropods a tendency for upward shift in altitude in their suitable climate space, while for bryophytes the shift was towards the coastal areas. Our results have profound implications for future conservation priorities on islands, such as for the redrawing of conservation borders of current protected areas.
Published: 2016

47. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

Author: Candido-dos-Reis, Francisco J, Song, Honglin, Goode, Ellen L, Cunningham, Julie M, Fridley, Brooke L, Larson, Melissa C, Alsop, Kathryn, Dicks, Ed, Harrington, Patricia, Ramus, Susan J, de Fazio, Anna, Mitchell, Gillian, Fereday, Sian, Bolton, Kelly L, Gourley, Charlie, Michie, Caroline, Karlan, Beth, Lester, Jenny, Walsh, Christine, Cass, Ilana, Olsson, Håkan, Gore, Martin, Benitez, Javier J, Garcia, Maria J, Andrulis, Irene, Mulligan, Anna Marie, Glendon, Gord, Blanco, Ignacio, Lazaro, Conxi, Whittemore, Alice S, McGuire, Valerie, Sieh, Weiva, Montagna, Marco, Alducci, Elisa, Sadetzki, Siegal, Chetrit, Angela, Kwong, Ava, Kjaer, Susanne K, Jensen, Allan, Høgdall, Estrid, Neuhausen, Susan, Nussbaum, Robert, Daly, Mary, Greene, Mark H, Mai, Phuong L, Loud, Jennifer T, Moysich, Kirsten, Toland, Amanda E, Lambrechts, Diether, Ellis, Steve, Candido-dos-Reis, Francisco J, Song, Honglin, Goode, Ellen L, Cunningham, Julie M, Fridley, Brooke L, Larson, Melissa C, Alsop, Kathryn, Dicks, Ed, Harrington, Patricia, Ramus, Susan J, de Fazio, Anna, Mitchell, Gillian, Fereday, Sian, Bolton, Kelly L, Gourley, Charlie, Michie, Caroline, Karlan, Beth, Lester, Jenny, Walsh, Christine, Cass, Ilana, Olsson, Håkan, Gore, Martin, Benitez, Javier J, Garcia, Maria J, Andrulis, Irene, Mulligan, Anna Marie, Glendon, Gord, Blanco, Ignacio, Lazaro, Conxi, Whittemore, Alice S, McGuire, Valerie, Sieh, Weiva, Montagna, Marco, Alducci, Elisa, Sadetzki, Siegal, Chetrit, Angela, Kwong, Ava, Kjaer, Susanne K, Jensen, Allan, Høgdall, Estrid, Neuhausen, Susan, Nussbaum, Robert, Daly, Mary, Greene, Mark H, Mai, Phuong L, Loud, Jennifer T, Moysich, Kirsten, Toland, Amanda E, Lambrechts, Diether, and Ellis, Steve
Abstract: PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
Published: 2015

48. Influencia de la etiología sobre la mortalidad en la insuficiencia cardíaca con función sistólica preservada en una población con alta prevalencia de cardiopatía chagásica

Author: Borges dos Reis, Francisco, Fernándes, André M., de Andrade, Gustavo M., Bitencourt, Almir, Neves, Flavia, Franca, Víctor H., Macedo, Cristiano R.B, Cruz Alves, Cristiano, Braga, Julio, Aras, Roque, Borges dos Reis, Francisco, Fernándes, André M., de Andrade, Gustavo M., Bitencourt, Almir, Neves, Flavia, Franca, Víctor H., Macedo, Cristiano R.B, Cruz Alves, Cristiano, Braga, Julio, and Aras, Roque
Abstract: Introducción La insuficiencia cardíaca con función sistólica preservada es un síndrome clínico con los mismos signos y síntomas de la insuficiencia cardíaca clásica. La enfermedad de Chagas es una causa importante de insuficiencia cardíaca en América Latina, que se asocia con miocardiopatía dilatada y deterioro progresivo de la función sistólica. No existen estudios previos que hayan evaluado pacientes con insuficiencia cardíaca y función sistólica preservada de una zona endémica en la cual la enfermedad de Chagas es la causa principal de insuficiencia cardíaca. Objetivo Comparar las características clínicas y la evolución de la insuficiencia cardíaca en pacientes con disfunción sistólica y con función sistólica preservada en una población con alta prevalencia de enfermedad de Chagas. Material y métodos Se realizó una evaluación prospectiva de los pacientes con diagnóstico clínico de insuficiencia cardíaca que ingresaron a un centro de referencia en Salvador, Bahía (Brasil). Se consideró función sistólica preservada a una fracción de eyección del ventrículo izquierdo mayor del 45% por ecocardiograma. Se realizó seguimiento al año a través de contacto telefónico o entrevista personal en el consultorio de insuficiencia cardíaca. Resultados Se incluyeron 383 pacientes durante un período de 16 meses; el 52,5% eran hombres y la edad media fue de 54,2 años. La función sistólica estuvo preservada en 138 pacientes (36%). La enfermedad de Chagas fue la principal etiología de ambos tipos de insuficiencia cardíaca (45,3% con disfunción sistólica y 44,2% con función sistólica preservada). El 93,5% (358) de los pacientes completaron un año de seguimiento. Los pacientes con enfermedad de Chagas y función sistólica preservada tuvieron menor mortalidad que los pacientes con disfunción sistólica (10% vs. 23,6%; p = 0,039). En los pacientes sin enfermedad de Chagas y función sistólica preservada, la mortalidad fue similar a la de aquellos con disfunción sistólica (10,4% vs. 15,8%; p
Published: 2013

49. Influencia de la etiología sobre la mortalidad en la insuficiencia cardíaca con función sistólica preservada en una población con alta prevalencia de cardiopatía chagásica

Author: Borges dos Reis, Francisco, Fernándes, André M., de Andrade, Gustavo M., Bitencourt, Almir, Neves, Flavia, Franca, Víctor H., Macedo, Cristiano R.B, Cruz Alves, Cristiano, Braga, Julio, Aras, Roque, Borges dos Reis, Francisco, Fernándes, André M., de Andrade, Gustavo M., Bitencourt, Almir, Neves, Flavia, Franca, Víctor H., Macedo, Cristiano R.B, Cruz Alves, Cristiano, Braga, Julio, and Aras, Roque
Abstract: Introducción La insuficiencia cardíaca con función sistólica preservada es un síndrome clínico con los mismos signos y síntomas de la insuficiencia cardíaca clásica. La enfermedad de Chagas es una causa importante de insuficiencia cardíaca en América Latina, que se asocia con miocardiopatía dilatada y deterioro progresivo de la función sistólica. No existen estudios previos que hayan evaluado pacientes con insuficiencia cardíaca y función sistólica preservada de una zona endémica en la cual la enfermedad de Chagas es la causa principal de insuficiencia cardíaca. Objetivo Comparar las características clínicas y la evolución de la insuficiencia cardíaca en pacientes con disfunción sistólica y con función sistólica preservada en una población con alta prevalencia de enfermedad de Chagas. Material y métodos Se realizó una evaluación prospectiva de los pacientes con diagnóstico clínico de insuficiencia cardíaca que ingresaron a un centro de referencia en Salvador, Bahía (Brasil). Se consideró función sistólica preservada a una fracción de eyección del ventrículo izquierdo mayor del 45% por ecocardiograma. Se realizó seguimiento al año a través de contacto telefónico o entrevista personal en el consultorio de insuficiencia cardíaca. Resultados Se incluyeron 383 pacientes durante un período de 16 meses; el 52,5% eran hombres y la edad media fue de 54,2 años. La función sistólica estuvo preservada en 138 pacientes (36%). La enfermedad de Chagas fue la principal etiología de ambos tipos de insuficiencia cardíaca (45,3% con disfunción sistólica y 44,2% con función sistólica preservada). El 93,5% (358) de los pacientes completaron un año de seguimiento. Los pacientes con enfermedad de Chagas y función sistólica preservada tuvieron menor mortalidad que los pacientes con disfunción sistólica (10% vs. 23,6%; p = 0,039). En los pacientes sin enfermedad de Chagas y función sistólica preservada, la mortalidad fue similar a la de aquellos con disfunción sistólica (10,4% vs. 15,8%; p
Published: 2013

50. The availability of teaching–pedagogical resources used for promotion of learning in teaching human anatomy

Author: AragÃ£o,JosÃ© Aderval, Fonseca-Barreto,Ana Terra, Brito,Ciro JosÃ©, Guerra,Danilo Ribeiro, Nunes-Mota,JosÃ© Carlos, Prado Reis,Francisco, AragÃ£o,JosÃ© Aderval, Fonseca-Barreto,Ana Terra, Brito,Ciro JosÃ©, Guerra,Danilo Ribeiro, Nunes-Mota,JosÃ© Carlos, and Prado Reis,Francisco
Abstract: José Aderval Aragão,1,5 Ana Terra Fonseca-Barreto,2 Ciro José Brito,1,3 Danilo Ribeiro Guerra,1 José Carlos Nunes-Mota,4 Francisco Prado Reis5 1Master's Degree Program in Physical Education, Universidade Federal de Sergipe (UFS), Aracaju, Sergipe, Brazil; 2School of Medicine, Universidade Federal de Sergipe (UFS), Aracaju, Sergipe, Brazil; 3Department of Physical Education, Universidade Federal de Sergipe (UFS), Aracaju, Sergipe, Brazil; 4Department of Morphology, (UFS), Aracaju, Sergipe, Brazil; 5School of Medicine, Universidade Tiradentes (UNIT), Aracaju, Sergipe, Brazil Abstract: Five hundred students attending higher education institutions in northeastern Brazil responded to questionnaires about their anatomy classes; students represented a variety of different health sciences disciplines. Analysis of the responses revealed the participation of teaching assistants in a large percentage of classes and the use of teaching resources, particularly images, from conventional radiographs to magnetic resonance images. The number of classes for cadaver dissection and the number of students with access to that type of class were small. In most cases, dissection was performed according to anatomic regions or systems. Medicine and nursing students had the highest number of practical dissection classes. Most students were assessed using practical and theoretical tests. Findings revealed conditions similar to those found elsewhere. Resources should be renewed and used to improve teaching for students whose courses demand the study of human anatomy. Keywords: educational assessments, gross anatomy, dissection, education medical undergraduate, anatomic models
Published: 2013

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