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2. A comprehensive immunohistochemical analysis of IMP2 and IMP3 in 542 cases of ovarian tumors

Author

Němejcová, Kristýna, Bártů, Michaela Kendall, Michálková, Romana, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Laco, Jan, Matěj, Radoslav, Méhes, Gábor, Singh, Naveena, Stolnicu, Simona, Škapa, Petr, Švajdler, Marián, Stružinská, Ivana, Cibula, David, Kocian, Roman, Lax, Sigurd F., McCluggage, W. Glenn, and Dundr, Pavel

Published
2023
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3. Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions)

Author

Elfgen, Constanze, Leo, Cornelia, Kubik-Huch, Rahel A., Muenst, Simone, Schmidt, Noemi, Quinn, Cecily, McNally, Sorcha, van Diest, Paul J., Mann, Ritse M, Bago-Horvath, Zsuzsanna, Bernathova, Maria, Regitnig, Peter, Fuchsjäger, Michael, Schwegler-Guggemos, Daniela, Maranta, Martina, Zehbe, Sabine, Tausch, Christoph, Güth, Uwe, Fallenberg, Eva Maria, Schrading, Simone, Kothari, Ashutosh, Sonnenschein, Martin, Kampmann, Gert, Kulka, Janina, Tille, Jean-Christophe, Körner, Meike, Decker, Thomas, Lax, Sigurd F., Daniaux, Martin, Bjelic-Radisic, Vesna, Kacerovsky-Strobl, Stephanie, Condorelli, Rosaria, Gnant, Michael, and Varga, Zsuzsanna

Published
2023
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4. Microsatellite instability in non-endometrioid ovarian epithelial tumors: a study of 400 cases comparing immunohistochemistry, PCR, and NGS based testing with mutation status of MMR genes

Author

Hájková, Nikola, Bártů, Michaela Kendall, Cibula, David, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Frühauf, Filip, Hausnerová, Jitka, Hojný, Jan, Krkavcová, Eva, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, Méhes, Gábor, Michálková, Romana, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Švajdler, Marián, Zima, Tomáš, McCluggage, Wilson Glenn, Stružinská, Ivana, and Dundr, Pavel

Published
2023
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5. Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance

Author

Dundr, Pavel, Hájková, Nikola, Kendall Bártů, Michaela, Cibula, David, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Frühauf, Filip, Hausnerová, Jitka, Hojný, Jan, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, Méhes, Gábor, Michálková, Romana, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Švajdler, Marián, Zima, Tomáš, McCluggage, W. Glenn, and Stružinská, Ivana

Published
2023
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7. The cytokeratin 17 expression in primary ovarian tumors has diagnostic but not prognostic significance

Author

Dundr, Pavel, Bazalová, Barbora, Bártů, Michaela, Bosse, Tjalling, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Jakša, Radek, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, McCluggage, W. Glenn, Méhes, Gábor, Michálková, Romana, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Škapa, Petr, Švajdler, Marián, and Stružinská, Ivana

Published
2022
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8. Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories

Author

Dundr, Pavel, Bártů, Michaela, Bosse, Tjalling, Bui, Quang Hiep, Cibula, David, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Hojný, Jan, Hájková, Nikola, Jakša, Radek, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, Méhes, Gábor, Michálková, Romana, Šafanda, Adam, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Švajdler, Marián, Zima, Tomáš, Stružinská, Ivana, and McCluggage, W. Glenn

Published
2023
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15. Neuroendocrine Marker Expression in Primary Non-neuroendocrine Epithelial Tumors of the Ovary: A Study of 551 Cases.

Author

Bártů, Michaela Kendall, Němejcová, Kristýna, Michálková, Romana, Quang Hiep Bui, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Laco, Jan, Matěj, Radoslav, Méhes, Gábor, Šafanda, Adam, Singh, Naveena, Škapa, Petr, Špůrková, Zuzana, Stolnicu, Simona, Švajdler, Marián, Lax, Sigurd F., McCluggage, W. Glenn, and Dundr, Pavel

Published
2024
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16. Clinical Behavior and Molecular Landscape of Stage I p53-abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

Jamieson, Amy, primary, Vermij, Lisa, additional, Kramer, Claire J.H., additional, Jobsen, Jan J., additional, Jürgenliemk-Schulz, Ina, additional, Lutgens, Ludy, additional, Mens, Jan Willem, additional, Haverkort, Marie A.D., additional, Slot, Annerie, additional, Nout, Remi A., additional, Oosting, Jan, additional, Carlson, Joseph, additional, Howitt, Brooke E., additional, Ip, Philip P.C., additional, Lax, Sigurd F., additional, McCluggage, W. Glenn, additional, Singh, Naveena, additional, McAlpine, Jessica N., additional, Creutzberg, Carien L., additional, Horeweg, Nanda, additional, Gilks, C. Blake, additional, and Bosse, Tjalling, additional

Published
2023
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17. A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer

Author

Kendzia, Sandra, primary, Franke, Susanne, additional, Kröhler, Tarek, additional, Golob-Schwarzl, Nicole, additional, Schweiger, Caroline, additional, Toeglhofer, Anna M., additional, Skofler, Christina, additional, Uranitsch, Stefan, additional, El-Heliebi, Amin, additional, Fuchs, Julia, additional, Punschart, Andreas, additional, Stiegler, Philipp, additional, Keil, Marlen, additional, Hoffmann, Jens, additional, Henderson, David, additional, Lehrach, Hans, additional, Yaspo, Marie-Laure, additional, Reinhard, Christoph, additional, Schäfer, Reinhold, additional, Keilholz, Ulrich, additional, Regenbrecht, Christian, additional, Schicho, Rudolf, additional, Fickert, Peter, additional, Lax, Sigurd F., additional, Erdmann, Frank, additional, Schulz, Marcel H., additional, Kiemer, Alexandra K., additional, Haybaeck, Johannes, additional, and Kessler, Sonja M., additional

Published
2023
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18. Neuroendocrine Marker Expression in Primary Non-neuroendocrine Epithelial Tumors of the Ovary: A Study of 551 Cases

Author

Kendall Bártů, Michaela, Němejcová, Kristýna, Michálková, Romana, Bui, Quang Hiep, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Laco, Jan, Matěj, Radoslav, Méhes, Gábor, Šafanda, Adam, Singh, Naveena, Škapa, Petr, Špůrková, Zuzana, Stolnicu, Simona, Švajdler, Marián, Lax, Sigurd F., McCluggage, W. Glenn, and Dundr, Pavel

Abstract

Expression of neuroendocrine (NE) markers in primary ovarian non-NE epithelial tumors has rarely been evaluated. The aim of our study was to evaluate the expression of the most widely used NE markers in these neoplasms and to determine any prognostic significance of NE marker expression. The cohort consisted of 551 primary ovarian tumors, including serous borderline tumors, low-grade serous carcinomas, high-grade serous carcinomas (HGSC), clear cell carcinomas, endometroid carcinomas, mucinous borderline tumors, and mucinous carcinomas. Immunohistochemical analysis was performed using antibodies against INSM1, synaptophysin, chromogranin, and CD56 on tissue microarray. Positivity for INSM1, synaptophysin, chromogranin, and CD56 was most frequently observed in mucinous tumors (48.7%, 26.0%, 41.5%, and 100%, respectively). The positivity for these NE markers was mostly restricted to nonmucinous elements distributed throughout the tumor. The mucinous borderline tumor and mucinous carcinomas groups had similar proportions of positivity (mucinous borderline tumor: 53%, mucinous carcinomas: 39%). In the other tumor types, except for HGSC, there was only focal expression (5%–10%) or negativity for NE markers. HGSC showed high CD56 expression (in 26% of cases). Survival analysis was only performed for CD56 in HGSC as this was the only group with sufficient positive cases, and it showed no prognostic significance. Except for mucinous tumors, expression of NE markers in non-NE ovarian epithelial tumors is low. CD56 expression in HGSC occurs frequently but is without diagnostic or prognostic value.

Published
2024
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19. A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer

Author

Kendzia, Sandra, Franke, Susanne Lieselotte, Kröhler, Tarek, Golob-Schwarzl, Nicole, Schweiger, Caroline, Toeglhofer, Anna M., Skofler, Christina, Uranitsch, Stefan, El-Heliebi, Amin, Fuchs, Julia, Punschart, Andreas, Stiegler, Philipp, Keil, Marlen, Hoffmann, Jens, Henderson, David, Lehrach, Hans, Yaspo, Marie-Laure, Reinhard, Christoph, Schäfer, Reinhold, Keilholz, Ulrich, Regenbrecht, Christian René Alexander, Schicho, Rudolf, Fickert, Peter, Lax, Sigurd F., Erdmann, Frank, Schulz, Marcel Holger, Kiemer, Alexandra Kathrin, Haybäck, Johannes, and Keßler, Sonja

Subjects
Drug resistance, Neoplasm, RNA-binding proteins, Colorectal neoplasms
Abstract

Aim: Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. Methods: Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. Results: We identified IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was significantly associated with resistance to selumetinib, gefitinib, and regorafenib in PDOs and to 5-fluorouracil and oxaliplatin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabilization of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confirmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. Conclusions: IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mitochondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance.

Published
2023
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20. Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

Jamieson, Amy, Vermij, Lisa, Kramer, Claire J.H., Jobsen, Jan J., Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A.D., Slot, Annerie, Nout, Remi A., Oosting, Jan, Carlson, Joseph, Howitt, Brooke E., Ip, Philip P.C., Lax, Sigurd F., McCluggage, W. Glenn, Singh, Naveena, McAlpine, Jessica N., Creutzberg, Carien L., Horeweg, Nanda, Gilks, C. Blake, Bosse, Tjalling, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J.H., Jobsen, Jan J., Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A.D., Slot, Annerie, Nout, Remi A., Oosting, Jan, Carlson, Joseph, Howitt, Brooke E., Ip, Philip P.C., Lax, Sigurd F., McCluggage, W. Glenn, Singh, Naveena, McAlpine, Jessica N., Creutzberg, Carien L., Horeweg, Nanda, Gilks, C. Blake, and Bosse, Tjalling

Abstract

PURPOSE: The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort. EXPERIMENTAL DESIGN: Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan-Meier method was used for survival analysis. RESULTS: We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, PIK3CA and PTEN mutations) but they also showed features of p53abn EC (TP53 mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients. CONCLUSIONS:A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence.

Published
2023

21. Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

MS Radiotherapie, Cancer, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J H, Jobsen, Jan J, Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A D, Slot, Annerie, Nout, Remi A, Oosting, Jan, Carlson, Joseph, Howitt, Brooke E, Ip, Philip P C, Lax, Sigurd F, McCluggage, W Glenn, Singh, Naveena, McAlpine, Jessica N, Creutzberg, Carien L, Horeweg, Nanda, Gilks, C Blake, Bosse, Tjalling, MS Radiotherapie, Cancer, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J H, Jobsen, Jan J, Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A D, Slot, Annerie, Nout, Remi A, Oosting, Jan, Carlson, Joseph, Howitt, Brooke E, Ip, Philip P C, Lax, Sigurd F, McCluggage, W Glenn, Singh, Naveena, McAlpine, Jessica N, Creutzberg, Carien L, Horeweg, Nanda, Gilks, C Blake, and Bosse, Tjalling

Published
2023

22. Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions)

Author

Pathologie, Cancer, Elfgen, Constanze, Leo, Cornelia, Kubik-Huch, Rahel A., Muenst, Simone, Schmidt, Noemi, Quinn, Cecily, McNally, Sorcha, van Diest, Paul J., Mann, Ritse M., Bago-Horvath, Zsuzsanna, Bernathova, Maria, Regitnig, Peter, Fuchsjäger, Michael, Schwegler-Guggemos, Daniela, Maranta, Martina, Zehbe, Sabine, Tausch, Christoph, Güth, Uwe, Fallenberg, Eva Maria, Schrading, Simone, Kothari, Ashutosh, Sonnenschein, Martin, Kampmann, Gert, Kulka, Janina, Tille, Jean Christophe, Körner, Meike, Decker, Thomas, Lax, Sigurd F., Daniaux, Martin, Bjelic-Radisic, Vesna, Kacerovsky-Strobl, Stephanie, Condorelli, Rosaria, Gnant, Michael, Varga, Zsuzsanna, Pathologie, Cancer, Elfgen, Constanze, Leo, Cornelia, Kubik-Huch, Rahel A., Muenst, Simone, Schmidt, Noemi, Quinn, Cecily, McNally, Sorcha, van Diest, Paul J., Mann, Ritse M., Bago-Horvath, Zsuzsanna, Bernathova, Maria, Regitnig, Peter, Fuchsjäger, Michael, Schwegler-Guggemos, Daniela, Maranta, Martina, Zehbe, Sabine, Tausch, Christoph, Güth, Uwe, Fallenberg, Eva Maria, Schrading, Simone, Kothari, Ashutosh, Sonnenschein, Martin, Kampmann, Gert, Kulka, Janina, Tille, Jean Christophe, Körner, Meike, Decker, Thomas, Lax, Sigurd F., Daniaux, Martin, Bjelic-Radisic, Vesna, Kacerovsky-Strobl, Stephanie, Condorelli, Rosaria, Gnant, Michael, and Varga, Zsuzsanna

Published
2023

23. Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions)

Author

Elfgen, Constanze; https://orcid.org/0000-0001-6092-6612, Leo, Cornelia; https://orcid.org/0000-0003-1601-0281, Kubik-Huch, Rahel A; https://orcid.org/0000-0002-3636-8697, Muenst, Simone, Schmidt, Noemi, Quinn, Cecily, McNally, Sorcha, van Diest, Paul J, Mann, Ritse M, Bago-Horvath, Zsuzsanna; https://orcid.org/0000-0002-8555-7806, Bernathova, Maria, Regitnig, Peter, Fuchsjäger, Michael, Schwegler-Guggemos, Daniela, Maranta, Martina, Zehbe, Sabine, Tausch, Christoph, Güth, Uwe; https://orcid.org/0000-0002-1849-5131, Fallenberg, Eva Maria, Schrading, Simone, Kothari, Ashutosh, Sonnenschein, Martin, Kampmann, Gert, Kulka, Janina, Tille, Jean-Christoph, Körner, Meike, Decker, Thomas, Lax, Sigurd F, Daniaux, Martin, Varga, Zsuzsanna; https://orcid.org/0000-0002-2855-983X, et al, Elfgen, Constanze; https://orcid.org/0000-0001-6092-6612, Leo, Cornelia; https://orcid.org/0000-0003-1601-0281, Kubik-Huch, Rahel A; https://orcid.org/0000-0002-3636-8697, Muenst, Simone, Schmidt, Noemi, Quinn, Cecily, McNally, Sorcha, van Diest, Paul J, Mann, Ritse M, Bago-Horvath, Zsuzsanna; https://orcid.org/0000-0002-8555-7806, Bernathova, Maria, Regitnig, Peter, Fuchsjäger, Michael, Schwegler-Guggemos, Daniela, Maranta, Martina, Zehbe, Sabine, Tausch, Christoph, Güth, Uwe; https://orcid.org/0000-0002-1849-5131, Fallenberg, Eva Maria, Schrading, Simone, Kothari, Ashutosh, Sonnenschein, Martin, Kampmann, Gert, Kulka, Janina, Tille, Jean-Christoph, Körner, Meike, Decker, Thomas, Lax, Sigurd F, Daniaux, Martin, Varga, Zsuzsanna; https://orcid.org/0000-0002-2855-983X, and et al

Abstract

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH.

Published
2023

24. Data Set for the Reporting of Endometrial Cancer: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Author

Matias-Guiu, Xavier, primary, Selinger, Christina I., additional, Anderson, Lyndal, additional, Buza, Natalia, additional, Ellenson, Lora H., additional, Fadare, Oluwole, additional, Ganesan, Raji, additional, Ip, Philip P.C., additional, Palacios, Jose, additional, Parra-Herran, Carlos, additional, Raspollini, Maria R., additional, Soslow, Robert A., additional, Werner, Henrica M.J., additional, Lax, Sigurd F., additional, and McCluggage, W. Glenn, additional

Published
2022
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25. Dataset for the Reporting of Gestational Trophoblastic Neoplasia: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Author

Hui, Pei, primary, Webster, Fleur, additional, Baergen, Rebecca N., additional, Buza, Natalia, additional, Cheung, Annie N.Y., additional, Kaur, Baljeet, additional, Ronnett, Brigitte M., additional, Shih, Ie-Ming, additional, Seckl, Michael J., additional, Lax, Sigurd F., additional, and McCluggage, W. Glenn, additional

Published
2022
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26. Data Set for the Reporting of Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Author

Gilks, C. Blake, primary, Selinger, Christina I., additional, Davidson, Ben, additional, Köbel, Martin, additional, Ledermann, Jonathan A., additional, Lim, Diana, additional, Malpica, Anais, additional, Mikami, Yoshiki, additional, Singh, Naveena, additional, Srinivasan, Radhika, additional, Vang, Russell, additional, Lax, Sigurd F., additional, and McCluggage, W. Glenn, additional

Published
2022
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27. Data Set for the Reporting of Carcinomas of the Vulva: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Author

Hoang, Lynn, primary, Webster, Fleur, additional, Bosse, Tjalling, additional, Focchi, Gustavo, additional, Gilks, C. Blake, additional, Howitt, Brooke E., additional, McAlpine, Jessica N., additional, Ordi, Jaume, additional, Singh, Naveena, additional, Wong, Richard Wing-Cheuk, additional, Lax, Sigurd F., additional, and McCluggage, W. Glenn, additional

Published
2022
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28. Data Set for Reporting of Uterine Malignant and Potentially Malignant Mesenchymal Tumors: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Author

Nucci, Marisa R., primary, Webster, Fleur, additional, Croce, Sabrina, additional, George, Suzanne, additional, Howitt, Brooke E., additional, Ip, Philip P.C., additional, Lee, Cheng-Han, additional, Rabban, Joseph T., additional, Soslow, Robert A., additional, van der Griend, Rachael, additional, Lax, Sigurd F., additional, and McCluggage, W. Glenn, additional

Published
2022
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29. Dataset for the Reporting of Carcinoma of the Cervix: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Author

Park, Kay J., primary, Selinger, Christina I., additional, Alvarado-Cabrero, Isabel, additional, Duggan, Máire A., additional, Kiyokawa, Takako, additional, Mills, Anne M., additional, Ordi, Jaume, additional, Otis, Christopher N., additional, Plante, Marie, additional, Stolnicu, Simona, additional, Talia, Karen L., additional, Wiredu, Edwin K., additional, Lax, Sigurd F., additional, and McCluggage, W. Glenn, additional

Published
2022
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30. Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53mutation status, but p53 expression/TP53status lack prognostic significance

Author

Dundr, Pavel, Hájková, Nikola, Kendall Bártů, Michaela, Cibula, David, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Frühauf, Filip, Hausnerová, Jitka, Hojný, Jan, Laco, Jan, Lax, Sigurd F., Matěj, Radoslav, Méhes, Gábor, Michálková, Romana, Němejcová, Kristýna, Singh, Naveena, Stolnicu, Simona, Švajdler, Marián, Zima, Tomáš, McCluggage, W. Glenn, and Stružinská, Ivana

Abstract

In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC. We assessed p53 expression for the three recognised patterns of aberrant staining in ovarian carcinoma [overexpression (‘all’), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tumours (strong nuclear p53 staining in ≥12 consecutive tumour cells) and correlated the results with next generation sequencing (NGS) in all qualitatively sufficient cases (92/123). Aberrant p53 expression was present in 25/75 (33.3%) MBT, 23/33 (69.7%) MC (75% of MC with expansile invasion and 61.5% with infiltrative invasion), and 10/15 (66.7%) tumours equivocal between MBT and MC. Regarding the 92 tumours with paired IHC and mutation results, 86 showed concordant results and six cases were discordant. Three discordant MBT cases showed aberrant expression but were TP53wild-type on sequencing. Three cases had normal p53 expression but contained a TP53mutation. Overall, IHC predicted the TP53mutation status with high sensitivity (94.1%) and specificity (92.7%). The accuracy of IHC was 93.5% with a positive predictive value of 94.1% and a negative predictive value of 92.7%. When comparing MC cases with wild-type TP53versus those with TP53mutation, there were no significant differences concerning disease-free survival, local recurrence-free survival, or metastases-free survival (p>0.05). In the MBT subgroup, there were no events for survival analyses. In conclusion, using an independent large sample set of ovarian mucinous tumours, the results of our study confirm that the suggested refined cut-off of strong nuclear p53 staining in ≥12 consecutive tumour cells reflect high accuracy, sensitivity and specificity for an underlying TP53mutation but the TP53mutation status has no prognostic significance in either MC or MBT.

Published
2023
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32. Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer.

Author

Singer CF, Holst F, Steurer S, Burandt EC, Lax SF, Jakesz R, Rudas M, Stöger H, Greil R, Sauter G, Filipits M, Simon R, and Gnant M

Subjects
Antineoplastic Agents, Hormonal therapeutic use, Estrogen Receptor alpha genetics, Estrogen Receptor alpha metabolism, Female, Gene Amplification, Humans, Postmenopause genetics, Prognosis, Prospective Studies, Tamoxifen therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology, Endocrine Gland Neoplasms genetics
Abstract

Purpose: Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer., Experimental Design: 394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERα expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indicating focal copy number alterations., Results: Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26-0.91; P = 0.02] and breast cancer-specific survival (adjusted HR 0.47; 95% CI, 0.27-0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 test), but was not prognostic by itself., Conclusions: Focal ESR1 amplification is an independent and powerful predictor for long-term distant recurrence-free and breast cancer-specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received tamoxifen for 5 years., (©2022 The Authors; Published by the American Association for Cancer Research.)

Published
2022
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