133 results on '"Tessier‐Cloutier, Basile"'
Search Results
102. Significance of p53 immunostaining in mesothelial proliferations and correlation with TP53mutation status
- Author
-
Naso, Julia R., Tessier-Cloutier, Basile, Senz, Janine, Huntsman, David G., and Churg, Andrew
- Abstract
p53 immunohistochemistry has long been proposed for the separation of benign from malignant mesothelial proliferations, with the older literature suggesting that any degree of positivity supported a diagnosis of mesothelioma. However, using modern immunohistochemistry platforms in other organ systems, notably gynecologic tumors, it has become clear that p53 staining can represent wild-type protein, and only specific staining patterns (absent, overexpression, or cytoplasmic expression) are indicative of a TP53mutation. We applied these principles to two tissue microarrays containing 94 mesotheliomas and 66 reactive mesothelial proliferations. Seven/65 (11%) epithelioid mesotheliomas showed aberrant staining (four absent and three overexpression patterns) as did 5/29 (17%) of sarcomatoid mesotheliomas (all overexpression patterns). We sequenced the TP53gene (exons 2–11) in five of the epithelioid and three of the sarcomatoid cases with aberrant staining as well as 12 epithelioid and eight sarcomatoid mesotheliomas with wild-type staining. All three sarcomatoid cases with aberrant staining showed mutated TP53, as did three of the epithelioid cases; in two of the epithelioid cases no mutation was detected, most likely because of large deletions not detected by this assay. In contrast, none of the 20 mesotheliomas with wild-type staining contained mutated TP53. We conclude that absent or overexpression p53 staining patterns can be used as a marker of a malignant vs. a benign mesothelial proliferation. The sensitivity of p53 staining by itself is low, but here addition of p53 to BAP1/MTAP staining increased sensitivity from 72 to 81% for epithelioid and 38 to 50% for sarcomatoid mesotheliomas.
- Published
- 2022
- Full Text
- View/download PDF
103. SWI/SNF‐deficiency defines highly aggressive undifferentiated endometrial carcinoma.
- Author
-
Tessier‐Cloutier, Basile, Coatham, Mackenzie, Carey, Mark, Nelson, Gregg S, Hamilton, Sarah, Lum, Amy, Soslow, Robert A, Stewart, Colin JR, Postovit, Lynne M, Köbel, Martin, and Lee, Cheng‐Han
- Subjects
ENDOMETRIAL cancer ,CARCINOMA ,NURSING care facilities ,PROTEIN deficiency ,PROGNOSIS ,NEOADJUVANT chemotherapy - Abstract
Dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UEC) is an endometrial cancer characterized by the presence of histologically undifferentiated carcinoma. Genomic inactivation of core switch/sucrose nonfermentable (SWI/SNF) complex proteins was recently identified in approximately two‐thirds of DDEC/UEC. The aim of this study was to delineate the clinical behavior of SWI/SNF‐deficient DDEC/UEC in comparison to SWI/SNF‐intact DDEC/UEC. The study cohort consisted of 56 SWI/SNF‐deficient DDEC/UEC (2 POLE‐mutated), which showed either SMARCA4 (BRG1) loss, ARID1A/1B co‐loss, or SMARCB1 (INI1) loss in the undifferentiated tumor, and 26 SWI/SNF‐intact DDEC/UEC (4 POLE‐mutated). The average age at diagnosis was 61 years for patients with SWI/SNF‐deficient tumors and 64 years for SWI/SNF‐intact tumors. Mismatch repair (MMR) protein deficiency was seen in 66% of SWI/SNF‐deficient and 50% of SWI/SNF‐intact tumors. At initial presentation, 55% of patients with SWI/SNF‐deficient tumors had extrauterine disease spread in contrast to 38% of patients with SWI/SNF‐intact tumors. The 2‐year disease specific survival (DSS) for stages I and II disease was 65% for SWI/SNF deficient tumors relative to 100% for SWI/SNF‐intact tumors (p = 0.042). For patients with stages III and IV disease, the median survival was 4 months for SWI/SNF‐deficient tumors compared to 36 months for SWI/SNF‐intact tumors (p = 0.0003). All six patients with POLE‐mutated tumors, including one with stage IV SWI/SNF‐deficient tumor were alive with no evidence of disease. Among the patients with advanced stage SWI/SNF‐deficient tumors, 68% (21 of 31) received adjuvant or neoadjuvant chemotherapy (platinum/taxane‐based) and all except the patient with a POLE‐mutated tumor (20 of 21) experienced disease progression either during chemotherapy or within 4 months after its completion. These findings show that core SWI/SNF‐deficiency defines a highly aggressive group of undifferentiated cancer characterized by rapid disease progression that is refractory to conventional platinum/taxane‐based chemotherapy. This underscores the importance of accurate clinical recognition of this aggressive tumor and the need to consider alternative systemic therapy for these tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
104. Whole‐slide laser microdissection for tumour enrichment.
- Author
-
Coope, Robin JN, Schlosser, Colin, Corbett, Richard D, Pleasance, Stephen, Tessier‐Cloutier, Basile, Pandoh, Pawan, Kirk, Heather, Haile, Simon, Zhao, Yongjun, Mungall, Andrew J, and Marra, Marco A
- Subjects
MICRODISSECTION ,LASERS ,TUMORS ,NUCLEIC acids ,NUCLEOTIDE sequencing - Abstract
The practical application of genome‐scale technologies to precision oncology research requires flexible tissue processing strategies that can be used to differentially select both tumour and normal cell populations from formalin‐fixed, paraffin‐embedded tissues. As tumour sequencing scales towards clinical implementation, practical difficulties in scheduling and obtaining fresh tissue biopsies at scale, including blood samples as surrogates for matched 'normal' DNA, have focused attention on the use of formalin‐preserved clinical samples collected routinely for diagnostic purposes. In practice, such samples often contain both tumour and normal cells which, if correctly partitioned, could be used to profile both tumour and normal genomes, thus identifying somatic alterations. Here we report a semi‐automated method for laser microdissecting entire slide‐mounted tissue sections to enrich for cells of interest with sufficient yield for whole genome and transcriptome sequencing. Using this method, we demonstrated enrichment of tumour material from mixed tumour–normal samples by up to 67%. Leveraging new methods that allow for the extraction of high‐quality nucleic acids from small amounts of formalin‐fixed tissues, we further showed that the method was successful in yielding sequence data of sufficient quality for use in BC Cancer's Personalized OncoGenomics (POG) program. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
105. An Analysis of Cell-of-Origin in Diffuse Large B-Cell Lymphoma in Systemic Lupus Erythematosus, Including Molecular and Clinical Factors Associated with Survival
- Author
-
Tessier-Cloutier, Basile, Twa, David, Baecklund, Eva, Gascoyne, Randy, Johnson, Nathalie A., Backlin, Carin, Kamen, Diane L., Clarke, Ann E., Ramsey-Goldman, Rosalind, Lee, Jennifer L. F., Farinha, Pedro, Bernatsky, Sasha, Tessier-Cloutier, Basile, Twa, David, Baecklund, Eva, Gascoyne, Randy, Johnson, Nathalie A., Backlin, Carin, Kamen, Diane L., Clarke, Ann E., Ramsey-Goldman, Rosalind, Lee, Jennifer L. F., Farinha, Pedro, and Bernatsky, Sasha
- Published
- 2018
106. Re-expression of SMARCA4/BRG1 in small cell carcinoma of ovary, hypercalcemic type (SCCOHT) promotes an epithelial-like gene signature through an AP-1-dependent mechanism.
- Author
-
Orlando, Krystal Ann, Douglas, Amber K., Abudu, Aierken, Wang, Yemin, Tessier-Cloutier, Basile, Su, Weiping, Peters, Alec, Sherman, Larry S., Moore, Rayvon, Nguyen, Vinh, Negri, Gian Luca, Colborne, Shane, Morin, Gregg B., Kommoss, Friedrich, Lang, Jessica D., Hendricks, William P. D., Raupach, Elizabeth A., Pirrotte, Patrick, Huntsman, David G., and Trent, Jeffrey M.
- Published
- 2021
- Full Text
- View/download PDF
107. Abstract PR03: Arginine deprivation as a potential targeted therapy for clear cell ovarian carcinoma
- Author
-
Ji, Jennifer Xiao Ye, primary, Cochrane, Dawn R., additional, Tessier-Cloutier, Basile, additional, Hoang, Lien N., additional, Wang, Yikan, additional, Cheung, Angela, additional, Chow, Christine, additional, Colborne, Shane, additional, Hughes, Christopher, additional, Morin, Gregg B., additional, and Huntsman, David G., additional
- Published
- 2018
- Full Text
- View/download PDF
108. Abstract B46: DICER1 and FOXL2 mutations correlate with clinicopathologic features of ovarian Sertoli-Leydig cell tumors
- Author
-
Karnezis, Anthony N., primary, Wang, Yemin, additional, Magrill, Jamie, additional, Keul, Jacqueline, additional, Kommoss, Stefan, additional, Tessier-Cloutier, Basile, additional, Proctor, Lily, additional, Schmidt, Dietmar, additional, Gilks, C Blake, additional, Huntsman, David G., additional, and Kommoss, Friedrich, additional
- Published
- 2018
- Full Text
- View/download PDF
109. Abstract B39: The origins of endometriosis-associated cancers
- Author
-
Cochrane, Dawn, primary, Tessier-Cloutier, Basile, additional, Lawrence, Katherine, additional, Nazeran, Tayyebeh, additional, Karnezis, Anthony, additional, Salamanca, Clara, additional, Lee, Timothy, additional, Cheng, Angela, additional, McAlpine, Jessica, additional, Hoang, Lien, additional, Gilks, Blake, additional, and Huntsman, David, additional
- Published
- 2018
- Full Text
- View/download PDF
110. DICER1 hot-spot mutations in ovarian gynandroblastoma
- Author
-
Wang, Yemin, primary, Karnezis, Anthony N, additional, Magrill, Jamie, additional, Tessier-Cloutier, Basile, additional, Lum, Amy, additional, Senz, Janine, additional, Gilks, C Blake, additional, McCluggage, W Glenn, additional, Huntsman, David G, additional, and Kommoss, Friedrich, additional
- Published
- 2018
- Full Text
- View/download PDF
111. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer
- Author
-
Zhang, Allen W., primary, McPherson, Andrew, additional, Milne, Katy, additional, Kroeger, David R., additional, Hamilton, Phineas T., additional, Miranda, Alex, additional, Funnell, Tyler, additional, Little, Nicole, additional, de Souza, Camila P.E., additional, Laan, Sonya, additional, LeDoux, Stacey, additional, Cochrane, Dawn R., additional, Lim, Jamie L.P., additional, Yang, Winnie, additional, Roth, Andrew, additional, Smith, Maia A., additional, Ho, Julie, additional, Tse, Kane, additional, Zeng, Thomas, additional, Shlafman, Inna, additional, Mayo, Michael R., additional, Moore, Richard, additional, Failmezger, Henrik, additional, Heindl, Andreas, additional, Wang, Yi Kan, additional, Bashashati, Ali, additional, Grewal, Diljot S., additional, Brown, Scott D., additional, Lai, Daniel, additional, Wan, Adrian N.C., additional, Nielsen, Cydney B., additional, Huebner, Curtis, additional, Tessier-Cloutier, Basile, additional, Anglesio, Michael S., additional, Bouchard-Côté, Alexandre, additional, Yuan, Yinyin, additional, Wasserman, Wyeth W., additional, Gilks, C. Blake, additional, Karnezis, Anthony N., additional, Aparicio, Samuel, additional, McAlpine, Jessica N., additional, Huntsman, David G., additional, Holt, Robert A., additional, Nelson, Brad H., additional, and Shah, Sohrab P., additional
- Published
- 2018
- Full Text
- View/download PDF
112. Frequent loss of claudin‐4 expression in dedifferentiated and undifferentiated endometrial carcinomas
- Author
-
Tessier‐Cloutier, Basile, primary, Soslow, Robert A, additional, Stewart, Colin J R, additional, Köbel, Martin, additional, and Lee, Cheng‐Han, additional
- Published
- 2018
- Full Text
- View/download PDF
113. Formalin fixation increases deamination mutation signature but should not lead to false positive mutations in clinical practice
- Author
-
Prentice, Leah M., primary, Miller, Ruth R., additional, Knaggs, Jeff, additional, Mazloomian, Alborz, additional, Aguirre Hernandez, Rosalia, additional, Franchini, Patrick, additional, Parsa, Kourosh, additional, Tessier-Cloutier, Basile, additional, Lapuk, Anna, additional, Huntsman, David, additional, Schaeffer, David F., additional, and Sheffield, Brandon S., additional
- Published
- 2018
- Full Text
- View/download PDF
114. Cell of Origin (COO) of Diffuse Large B-Cell Lymphoma (DLBCL) in Patients with Systemic Lupus Erythematosus (SLE)
- Author
-
Tessier-Cloutier, Basile, Bernatsky, Sasha, Baecklund, Eva, Gascoyne, Randy, Johnson, Nathalie, Kamen, Diane L., Clarke, Ann E., Ramsey-Goldman, Rosalind, Lee, Jennifer L. F., Farinha, Pedro, Tessier-Cloutier, Basile, Bernatsky, Sasha, Baecklund, Eva, Gascoyne, Randy, Johnson, Nathalie, Kamen, Diane L., Clarke, Ann E., Ramsey-Goldman, Rosalind, Lee, Jennifer L. F., and Farinha, Pedro
- Abstract
Also published in Modern Pathology, Vol. 30, nr Suppl. 2, 381A-381A s., 1526 DOI: 10.1038/modpathol.2016.253Link to record in DiVA http://uu.diva-portal.org/smash/record.jsf?pid=diva2:1091820
- Published
- 2017
115. Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
- Author
-
Tessier-Cloutier, Basile, primary, Kalloger, Steve E., additional, Al-Kandari, Mohammad, additional, Milne, Katy, additional, Gao, Dongxia, additional, Nelson, Brad H., additional, Renouf, Daniel J., additional, Sheffield, Brandon S., additional, and Schaeffer, David F., additional
- Published
- 2017
- Full Text
- View/download PDF
116. Abstract 2215: Detection of novel markers of transitional cell carcinoma of the ovary, the TCC-like variant of high grade serous carcinoma, using proteomics and immunohistochemistry
- Author
-
Tessier-Cloutier, Basile, primary, Magrill, Jamie, additional, Kommoss, Stefan, additional, Gilks, Blake C., additional, Huntsman, David G., additional, Cochrane, Dawn R., additional, Talhouk, Aline, additional, Soslow, Robert, additional, Morin, Gregg B., additional, Hughes, Chris J., additional, Karnezis, Anthony N., additional, Chow, Christine, additional, Cheng, Angela S., additional, Bois, Andreas du, additional, Pfisterer, Jacobus, additional, and Kommoss, Friedrich, additional
- Published
- 2017
- Full Text
- View/download PDF
117. Cancer-Associated Mutations in Endometriosis without Cancer
- Author
-
Anglesio, Michael S., primary, Papadopoulos, Nickolas, additional, Ayhan, Ayse, additional, Nazeran, Tayyebeh M., additional, Noë, Michaël, additional, Horlings, Hugo M., additional, Lum, Amy, additional, Jones, Siân, additional, Senz, Janine, additional, Seckin, Tamer, additional, Ho, Julie, additional, Wu, Ren-Chin, additional, Lac, Vivian, additional, Ogawa, Hiroshi, additional, Tessier-Cloutier, Basile, additional, Alhassan, Rami, additional, Wang, Amy, additional, Wang, Yuxuan, additional, Cohen, Joshua D., additional, Wong, Fontayne, additional, Hasanovic, Adnan, additional, Orr, Natasha, additional, Zhang, Ming, additional, Popoli, Maria, additional, McMahon, Wyatt, additional, Wood, Laura D., additional, Mattox, Austin, additional, Allaire, Catherine, additional, Segars, James, additional, Williams, Christina, additional, Tomasetti, Cristian, additional, Boyd, Niki, additional, Kinzler, Kenneth W., additional, Gilks, C. Blake, additional, Diaz, Luis, additional, Wang, Tian-Li, additional, Vogelstein, Bert, additional, Yong, Paul J., additional, Huntsman, David G., additional, and Shih, Ie-Ming, additional
- Published
- 2017
- Full Text
- View/download PDF
118. Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and correlation with TP53mutation status
- Author
-
Tessier-Cloutier, Basile, Kortekaas, Kim E., Thompson, Emily, Pors, Jennifer, Chen, Julia, Ho, Julie, Prentice, Leah M., McConechy, Melissa K., Chow, Christine, Proctor, Lily, McAlpine, Jessica N., Huntsman, David G., Gilks, C. Blake, Bosse, Tjalling, and Hoang, Lynn N.
- Abstract
The recent literature has shown that vulvar squamous cell carcinoma (VSCC) can be stratified into two prognostically relevant groups based on human papillomavirus (HPV) status. The prognostic value of p53 for further sub-stratification, particularly in the HPV-independent group, has not been agreed upon. This disagreement is likely due to tremendous variations in p53 immunohistochemical (IHC) interpretation. To address this problem, we sought to compare p53 IHC patterns with TP53mutation status. We studied 61 VSCC (48 conventional VSCC, 2 VSCC with sarcomatoid features, and 11 verrucous carcinomas) and 42 in situ lesions (30 differentiated vulvar intraepithelial neoplasia [dVIN], 9 differentiated exophytic vulvar intraepithelial lesions [deVIL], and 3 high-grade squamous intraepithelial lesions or usual vulvar intraepithelial neoplasia [HSIL/uVIN]). IHC for p16 and p53, and sequencing of TP53exons 4–9 were performed. HPV in situ hybridization (ISH) was performed in selected cases. We identified six major p53 IHC patterns, two wild-type patterns: (1) scattered, (2) mid-epithelial expression (with basal sparing), and four mutant patterns: (3) basal overexpression, (4) parabasal/diffuse overexpression, (5) absent, and (6) cytoplasmic expression. These IHC patterns were consistent with TP53mutation status in 58/61 (95%) VSCC and 39/42 (93%) in situ lesions. Cases that exhibited strong scattered staining and those with a weak basal overexpression pattern could be easily confused. The mid-epithelial pattern was exclusively observed in p16-positive lesions; the basal and parabasal layers that had absent p53 staining, appeared to correlate with the cells that were positive for HPV-ISH. This study describes a pattern-based p53 IHC interpretation framework, which can be utilized as a surrogate marker for TP53mutational status in both VSCC and vulvar in situ lesions.
- Published
- 2020
- Full Text
- View/download PDF
119. Targeted Molecular Sequencing of Recurrent and Multifocal Non–HPV-associated Squamous Cell Carcinoma of the Vulva
- Author
-
Pors, Jennifer, Tessier-Cloutier, Basile, Thompson, Emily, Almadani, Noorah, Ho, Julie, Gilks, Blake, Huntsman, David, and Hoang, Lynn
- Abstract
Recurrent vulvar squamous cell carcinomas (SCCs) are a poorly understood and aggressive group of treatment-resistant neoplasms. Currently, it remains unclear whether these are in fact recurrences of the same primary tumor, or the development of entirely new tumors. Here, to address this question, we examined the mutational profile of a series of patients with recurrent or multifocal non–human papilloma virus (HPV)-associated vulvar SCC. We performed a targeted 33-gene next-generation sequencing panel on a series of 14 patients with recurrent or multifocal non–HPV-associated vulvar SCC and precursor neoplasms. This amounted to 54 cases (33 SCC, 1 verrucous carcinoma, 13 differentiated vulvar intraepithelial neoplasia, and 7 differentiated exophytic vulvar intraepithelial lesion), with 79 mutations detected altogether. TP53[51/79 (65%)] was the most frequently mutated gene. Mutations in PIK3CA[16/79 (20%)), HRAS[6/79 (8%)], PTEN[4/79 (5%)], EGFR[1/79 (1%)], and GNAS[1/79 (1%)] were occasionally seen. Most patients with SCC [5/9 (56%)] recurrent, 4/5 (80%) multifocal] demonstrated a clonal relationship, and harbored the same mutations in the same genes in metachronous or synchronous tumors. A subset of the recurrent tumors [2/5 (40%)] recurred with additional mutations. These clonal relationships were shared between SCC and differentiated vulvar intraepithelial neoplasia in each case. By contrast, a small number of recurrent tumors [3/9 (33%)] demonstrated novel mutations, entirely different from the primary tumor. Thus, our findings suggest that recurrent non–HPV-associated vulvar SCC can arise from 2 mechanisms.
- Published
- 2024
- Full Text
- View/download PDF
120. Mo2072 Endoscopic Ultrasound-Guided FNA and Sharkcore FNB in Sampling Solid Lesions
- Author
-
Kayal, Ahmed, primary, Tessier-Cloutier, Basile, additional, Chan, Christopher, additional, Weiss, Alan, additional, Byrne, Michael F., additional, Schaeffer, David, additional, Tan, Jonathan (Yong) C., additional, and Donnellan, Fergal, additional
- Published
- 2016
- Full Text
- View/download PDF
121. DICER1and FOXL2Mutation Status Correlates With Clinicopathologic Features in Ovarian Sertoli-Leydig Cell Tumors
- Author
-
Karnezis, Anthony N., Wang, Yemin, Keul, Jacqueline, Tessier-Cloutier, Basile, Magrill, Jamie, Kommoss, Stefan, Senz, Janine, Yang, Winnie, Proctor, Lily, Schmidt, Dietmar, Clement, Philip B., Gilks, C. Blake, Huntsman, David G., and Kommoss, Friedrich
- Abstract
Supplemental Digital Content is available in the text.Sertoli-Leydig cell tumors (SLCTs) are rare ovarian sex cord-stromal neoplasms. The only known recurrent genetic abnormality is DICER1mutation, with rare mutations reported in FOXL2. We set out to establish a molecular classifier using DICER1and FOXL2somatic mutation status and clinicopathologic features in 42 SLCTs. Five tumors (12%) were well differentiated, 31 (74%) moderately differentiated, and 6 (14%) poorly differentiated. Eight (19%) had heterologous elements, and 2 (5%) showed retiform differentiation; all 10 were moderately differentiated. DICER1RNase IIIb domain mutations were identified in 18/41 (44%; 17 moderately, 1 poorly differentiated), including all cases with retiform or heterologous elements. FOXL2c.402C>G(p.C134W) mutation was identified in 8/42 (19%) tumors (5 moderately, 3 poorly differentiated). DICER1and FOXL2mutations were mutually exclusive. Median age for the cohort was 47 years (range, 15 to 90 y). Patients with DICER1mutations were younger (median, 24.5 y; range, 15 to 62 y) than patients with FOXL2mutation (median, 79.5 y; range, 51 to 90 y) (P<0.0001). Nine of 10 tumors with retiform or heterologous elements occurred in premenopausal patients (median, 26.5 y; range, 15 to 57 y). Patients with tumors that were wild type for DICER1and FOXL2(15/42, 37%) had an intermediate age (median, 51 y; range, 17 to 74 y). All tumors were FOXL2 positive by immunohistochemistry. Patients with FOXL2mutation trended toward presenting more often with abnormal bleeding (P=0.13); DICER1-mutant patients trended toward having more androgenic symptoms (P=0.22). Our data suggest at least 3 molecular subtypes of SLCT with distinct clinicopathologic features: DICER1mutant (younger, more androgenic symptoms, moderately/poorly differentiated, retiform or heterologous elements), FOXL2mutant (postmenopausal, abnormal bleeding, moderately/poorly differentiated, no retiform or heterologous elements), and DICER1/FOXL2wild type (intermediate age, no retiform or heterologous elements, including all well-differentiated tumors).
- Published
- 2019
- Full Text
- View/download PDF
122. Systemic Lupus Erythematosus and Malignancies
- Author
-
Tessier-Cloutier, Basile, primary, Clarke, Ann E., additional, Ramsey-Goldman, Rosalind, additional, Gordon, Caroline, additional, Hansen, James E., additional, and Bernatsky, Sasha, additional
- Published
- 2014
- Full Text
- View/download PDF
123. Immunophenotypic features of dedifferentiated endometrial carcinoma - insights from BRG1/ INI1-deficient tumours.
- Author
-
Hoang, Lien N, Lee, Yow‐Shan, Karnezis, Anthony N, Tessier‐Cloutier, Basile, Almandani, Noorah, Coatham, Mackenzie, Gilks, C Blake, Soslow, Robert A, Stewart, Colin J R, Köbel, Martin, and Lee, Cheng‐Han
- Subjects
TREATMENT of endometrial cancer ,ENDOMETRIAL cancer ,IMMUNOPHENOTYPING ,ESTROGEN receptors ,GENETIC mutation ,IMMUNOSTAINING ,GENETICS - Abstract
Aims Dedifferentiated endometrial carcinoma ( DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 ( BRG1) and inactivation of SMARCB1 ( INI1) were recently described as potential mechanisms underlying the histological dedifferentiation. The aim of this study was to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histological and molecular features ( BRG1/ INI1 deficiency). Methods and results We evaluated PAX8, oestrogen receptor ( ER) and p53 immunostaining in the endometrioid and the undifferentiated components of 20 BRG1/ INI1-deficient DDECs and 15 BRG1/ INI1-intact DDECs, and compared the results with those of 23 grade 3 endometrioid carcinomas. The differentiated endometrioid component was positive for PAX8 and/or ER in 19 of 20 BRG1/ INI1-deficient DDECs, whereas the corresponding undifferentiated component of all 20 tumours showed a complete absence of PAX8 and ER staining. All except one of the BRG1/ INI1-deficient tumours showed a wild-type p53 staining pattern. PAX8 and ER expression in the undifferentiated component was absent in 67% and 80% of BRG1/ INI1-intact DDECs, respectively, whereas 47% of the BRG1/ INI1-intact DDECs showed a mutated p53 staining pattern. In comparison, absent PAX8 expression and absent ER expression were each observed in the more solid area of 48% and 48% of grade 3 endometrioid carcinomas. Conclusions The consistent absence of PAX8 and ER expression in molecularly defined ( BRG1/ INI1-deficient) DDECs suggests that the loss of PAX8 and ER expression is a fundamental feature of dedifferentiation. The frequent findings of a mutated p53 staining pattern in BRG1/ INI1-intact DDECs indicate that BRG1/ INI1-intact DDECs may be biologically different from BRG1/ INI1-deficient tumours. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
124. HER2genetic intratumor heterogeneity is associated with resistance to trastuzumab and trastuzumab emtansine therapy in recurrent high-grade endometrial cancer
- Author
-
Shen, Sherry, Ma, Weining, Brown, David, Da Cruz Paula, Arnaud, Zhou, Qin, Iaosonos, Alexia, Tessier-Cloutier, Basile, Ross, Dara S., Troso-Sandoval, Tiffany, Reis-Filho, Jorge S., Abu-Rustum, Nadeem, Zhang, Yanming, Ellenson, Lora H., Weigelt, Britta, Makker, Vicky, and Chui, M. Herman
- Abstract
Anti-HER2 targeted therapies have recently demonstrated clinical activity in the treatment of high-grade endometrial carcinomas (EC), particularly serous carcinomas with HER2amplification and/or overexpression. Intratumor heterogeneity of HER2amplification, or HER2genetic intratumor heterogeneity (G-ITH), has been associated with resistance to anti-HER2 therapies in breast and gastroesophageal cancers, however, its clinical relevance in EC is unknown. To characterize HER2G-ITH in EC, archival specimens from a clinically annotated cohort of 57 ECs treated with trastuzumab or trastuzumab-emtansine in the recurrent (n=38) or adjuvant (n=19) setting were subjected to central pathology review, HER2 assessment by immunohistochemistry (IHC) and fluorescence in-situhybridization (FISH), and next-generation sequencing (NGS). HER2G-ITH, defined as HER2amplification in 5%-50% of tumor cells examined by FISH, was identified in 36% (19/53) of ECs and was associated with lower HER2copy number and levels of protein expression. HER2 IHC revealed spatially distinct areas of strong expression juxtaposed with areas of low/absent expression in tumors with the “cluster” pattern of G-ITH, while the “mosaic” pattern was typically associated with a diffuse admixture of cells with variable levels of HER2 expression. HER2G-ITH was frequently observed in cases with IHC/FISH or FISH/NGS discrepancies and/or with an equivocal/negative FISH result (9/13, 69%). While the objective response rate to anti-HER2 therapy in recurrent ECs was 52% (13/25) for tumors lacking HER2G-ITH, none (0%, 0/10) of the patients with HER2G-ITH achieved a complete or partial response (p=0.005). HER2G-ITH was significantly associated with worse progression-free survival (HR 2.88 (95% CI 1.33-6.27), p=0.005), but not overall survival. HER2 IHC score, HER2/CEP17ratio, HER2copy number, histologic subtype, and other genetic alterations, including PIK3CAhotspot mutations, were not significantly associated with therapeutic response or survival outcomes. Treatment responses were not restricted to serous carcinomas, supporting consideration of anti-HER2 therapy in patients with HER2-positive high-grade ECs of non-serous histology. Our results demonstrate that HER2G-ITH is an important determinant of response to trastuzumab and trastuzumab-emtansine in EC, providing a rationale for development of novel therapeutic strategies to target HER2-non-amplified resistant tumor subpopulations, such as HER2 antibody drug conjugates with bystander effects.
- Published
- 2023
- Full Text
- View/download PDF
125. Pattern Based Interpretation of p53 Immunohistoschemistry as a Surrogate Marker for TP53 Mutations in Vulvar Squamous Cell Carcinoma
- Author
-
Kortekaas, Kim, Tessier-Cloutier, Basile, Rutten, Tessa, Poelgeest, Mariette, Hoang, Lynn, Gilks, C. Blake, and Tjalling Bosse
126. SWI/SNF-deficient undifferentiated malignancies: where to draw the line † .
- Author
-
Tessier-Cloutier B, Kleinman CL, and Foulkes WD
- Subjects
- Carcinoma, Ovarian Epithelial genetics, DNA Helicases genetics, DNA Methylation, Female, Humans, Nuclear Proteins genetics, SMARCB1 Protein genetics, Transcription Factors genetics, Carcinoma, Small Cell genetics, Ovarian Neoplasms genetics, Rhabdoid Tumor genetics
- Abstract
Alterations in chromatin remodelling genes are increasingly recognised as drivers of undifferentiated malignancies. In atypical teratoid/rhabdoid tumours (ATRTs) and extracranial rhabdoid tumours (ECRTs), inactivation of SMARCB1 underlies >95% of cases. In the remainder, the culprit is another SWI/SNF family member, SMARCA4. By contrast, in small cell carcinoma of the ovary hypercalcaemic type (SCCOHT), SMARCA4 deficiency is by far the most common driver mechanism, while SMARCB1 alterations are rarely seen. It is unclear why alterations are so heavily weighted towards one or another subunit based on site alone, but both have become essential markers for the diagnosis and management of these undifferentiated lesions. Core SMARCA4-deficient undifferentiated malignancies share an aggressive clinical course and show an overlapping morphologic phenotype. In their study, Andrianteranagna, Cyrta and colleagues used DNA methylation and gene expression profiling to compare two subsets of SMARCA4-deficient malignancies diagnosed as SCCOHT and ECRT. Their work gives further insight into the subtle molecular spectrum of SMARCA4-deficient tumours, and their distinction from ATRT and ECRT with SMARCB1 inactivation. The characterisation of these molecular features is likely to play an important role in the future as we try to establish a clinically meaningful framework for the diagnosis and management of these lesions. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
127. Arginine Depletion Therapy with ADI-PEG20 Limits Tumor Growth in Argininosuccinate Synthase-Deficient Ovarian Cancer, Including Small-Cell Carcinoma of the Ovary, Hypercalcemic Type.
- Author
-
Ji JX, Cochrane DR, Tessier-Cloutier B, Chen SY, Ho G, Pathak KV, Alcazar IN, Farnell D, Leung S, Cheng A, Chow C, Colborne S, Negri GL, Kommoss F, Karnezis A, Morin GB, McAlpine JN, Gilks CB, Weissman BE, Trent JM, Hoang L, Pirrotte P, Wang Y, and Huntsman DG
- Subjects
- Animals, Arginine antagonists & inhibitors, Arginine genetics, Argininosuccinate Synthase deficiency, Carcinoma, Small Cell genetics, Carcinoma, Small Cell pathology, Cell Line, Tumor, Cell Proliferation drug effects, Female, Humans, Mice, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Ovary metabolism, Ovary pathology, Parathyroid Hormone-Related Protein genetics, Parathyroid Hormone-Related Protein immunology, Proteomics, Xenograft Model Antitumor Assays, Argininosuccinate Synthase genetics, Carcinoma, Small Cell drug therapy, Hydrolases pharmacology, Ovarian Neoplasms drug therapy, Polyethylene Glycols pharmacology
- Abstract
Purpose: Many rare ovarian cancer subtypes, such as small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), have poor prognosis due to their aggressive nature and resistance to standard platinum- and taxane-based chemotherapy. The development of effective therapeutics has been hindered by the rarity of such tumors. We sought to identify targetable vulnerabilities in rare ovarian cancer subtypes., Experimental Design: We compared the global proteomic landscape of six cases each of endometrioid ovarian cancer (ENOC), clear cell ovarian cancer (CCOC), and SCCOHT to the most common subtype, high-grade serous ovarian cancer (HGSC), to identify potential therapeutic targets. IHC of tissue microarrays was used as validation of arginosuccinate synthase (ASS1) deficiency. The efficacy of arginine-depriving therapeutic ADI-PEG20 was assessed in vitro using cell lines and patient-derived xenograft mouse models representing SCCOHT., Results: Global proteomic analysis identified low ASS1 expression in ENOC, CCOC, and SCCOHT compared with HGSC. Low ASS1 levels were validated through IHC in large patient cohorts. The lowest levels of ASS1 were observed in SCCOHT, where ASS1 was absent in 12 of 31 cases, and expressed in less than 5% of the tumor cells in 9 of 31 cases. ASS1-deficient ovarian cancer cells were sensitive to ADI-PEG20 treatment regardless of subtype in vitro . Furthermore, in two cell line mouse xenograft models and one patient-derived mouse xenograft model of SCCOHT, once-a-week treatment with ADI-PEG20 (30 mg/kg and 15 mg/kg) inhibited tumor growth in vivo ., Conclusions: Preclinical in vitro and in vivo studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT., (©2020 American Association for Cancer Research.)
- Published
- 2020
- Full Text
- View/download PDF
128. Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and correlation with TP53 mutation status.
- Author
-
Tessier-Cloutier B, Kortekaas KE, Thompson E, Pors J, Chen J, Ho J, Prentice LM, McConechy MK, Chow C, Proctor L, McAlpine JN, Huntsman DG, Gilks CB, Bosse T, and Hoang LN
- Subjects
- Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Female, Humans, Immunohistochemistry methods, Mutation, Tumor Suppressor Protein p53 genetics, Vulvar Neoplasms genetics, Vulvar Neoplasms metabolism, Biomarkers, Tumor analysis, Carcinoma, Squamous Cell pathology, Tumor Suppressor Protein p53 metabolism, Vulvar Neoplasms pathology
- Abstract
The recent literature has shown that vulvar squamous cell carcinoma (VSCC) can be stratified into two prognostically relevant groups based on human papillomavirus (HPV) status. The prognostic value of p53 for further sub-stratification, particularly in the HPV-independent group, has not been agreed upon. This disagreement is likely due to tremendous variations in p53 immunohistochemical (IHC) interpretation. To address this problem, we sought to compare p53 IHC patterns with TP53 mutation status. We studied 61 VSCC (48 conventional VSCC, 2 VSCC with sarcomatoid features, and 11 verrucous carcinomas) and 42 in situ lesions (30 differentiated vulvar intraepithelial neoplasia [dVIN], 9 differentiated exophytic vulvar intraepithelial lesions [deVIL], and 3 high-grade squamous intraepithelial lesions or usual vulvar intraepithelial neoplasia [HSIL/uVIN]). IHC for p16 and p53, and sequencing of TP53 exons 4-9 were performed. HPV in situ hybridization (ISH) was performed in selected cases. We identified six major p53 IHC patterns, two wild-type patterns: (1) scattered, (2) mid-epithelial expression (with basal sparing), and four mutant patterns: (3) basal overexpression, (4) parabasal/diffuse overexpression, (5) absent, and (6) cytoplasmic expression. These IHC patterns were consistent with TP53 mutation status in 58/61 (95%) VSCC and 39/42 (93%) in situ lesions. Cases that exhibited strong scattered staining and those with a weak basal overexpression pattern could be easily confused. The mid-epithelial pattern was exclusively observed in p16-positive lesions; the basal and parabasal layers that had absent p53 staining, appeared to correlate with the cells that were positive for HPV-ISH. This study describes a pattern-based p53 IHC interpretation framework, which can be utilized as a surrogate marker for TP53 mutational status in both VSCC and vulvar in situ lesions.
- Published
- 2020
- Full Text
- View/download PDF
129. Tubo-Ovarian Transitional Cell Carcinoma and High-grade Serous Carcinoma Show Subtly Different Immunohistochemistry Profiles.
- Author
-
Magrill J, Karnezis AN, Tessier-Cloutier B, Talhouk A, Kommoss S, Cochrane D, Chow C, Cheng A, Soslow R, Hauptmann S, du Bois A, Pfisterer J, Gilks CB, Huntsman DG, and Kommoss F
- Subjects
- Carcinoma, Transitional Cell metabolism, Cohort Studies, Female, Humans, Immunohistochemistry, Ovarian Neoplasms metabolism, Tissue Array Analysis, Biomarkers, Tumor metabolism, Carcinoma, Transitional Cell pathology, Neoplasm Proteins metabolism, Ovarian Neoplasms pathology, Proteomics
- Abstract
Tubo-ovarian transitional cell carcinoma (TCC) is grouped with high-grade serous carcinoma (HGSC) in the current World Health Organization classification. TCC is associated with BRCA mutations and a better prognosis compared with HGSC. Previous papers examining the immunohistochemical features of TCC have studied limited numbers of samples. No marker reflecting the biological difference between TCC and HGSC is known. We collected a large cohort of TCC to determine whether TCC and HGSC could be distinguished by immunohistochemistry. A tissue microarray was built from 89 TCC and a control cohort of 232 conventional HGSC. Immunohistochemistry was performed, scored, and statistically analyzed for routine markers of HGSC and urothelial tumors: PAX8, WT1, p53, p16, ER, p63, and GATA3. Using scoring cutoffs commonly employed in clinical practice, the immunohistochemical profile of TCC was indistinguishable from HGSC for all markers. However, more detailed scoring criteria revealed statistically significant differences between the 2 groups of tumors with respect to ER, PAX8, and WT1. HGSC showed more diffuse and intense staining for PAX8 (P=0.004 and 0.001, respectively) and WT1 (P=0.002 and 0.002, respectively); conversely, TCC showed more intense staining for ER (P=0.007). TCC and HGSC therefore show subtle differences in their immunohistochemical profiles which might reflect underlying (epi)genetic differences. Further studies using proteomic analysis will focus on the identification of differentially expressed proteins that might serve as markers of TCC-like differentiation, which could help explain biologic differences between TCC and HGSC and might identify other cases of HGSC with a better prognosis.
- Published
- 2019
- Full Text
- View/download PDF
130. Detection and genomic characterization of a mammary-like adenocarcinoma.
- Author
-
Grewal JK, Eirew P, Jones M, Chiu K, Tessier-Cloutier B, Karnezis AN, Karsan A, Mungall A, Zhou C, Yip S, Tinker AV, Laskin J, Marra M, and Jones SJM
- Subjects
- Breast pathology, Breast Neoplasms genetics, Diagnosis, Differential, Female, Gene Expression Profiling, Genomics, Humans, Immunohistochemistry, Middle Aged, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Transcriptome, Whole Genome Sequencing, Adenocarcinoma genetics, Vulva pathology, Vulvar Neoplasms genetics
- Abstract
Whole-genome and transcriptome sequencing were performed to identify potential therapeutic strategies in the absence of viable treatment options for a patient initially diagnosed with vulvar adenocarcinoma. Genomic events were prioritized by comparison against variant distributions in the TCGA pan-cancer data set and complemented with detailed transcriptome sequencing and copy-number analysis. These findings were considered against published scientific literature in order to evaluate the functional effects of potentially relevant genomic events. Analysis of the transcriptome against a background of 27 TCGA cancer types led to reclassification of the tumor as a primary HER2
+ mammary-like adenocarcinoma of the vulva. This revised diagnosis was subsequently confirmed by follow-up immunohistochemistry for a mammary-like adenocarcinoma. The patient was treated with chemotherapy and targeted therapies for HER2+ breast cancer. The detailed pathology and genomic findings of this case are presented herein., (© 2017 Grewal et al.; Published by Cold Spring Harbor Laboratory Press.)- Published
- 2017
- Full Text
- View/download PDF
131. Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies.
- Author
-
Waters AM, Ozkan-Dagliyan I, Vaseva AV, Fer N, Strathern LA, Hobbs GA, Tessier-Cloutier B, Gillette WK, Bagni R, Whiteley GR, Hartley JL, McCormick F, Cox AD, Houghton PJ, Huntsman DG, Philips MR, and Der CJ
- Subjects
- Animals, Antineoplastic Agents, Immunological analysis, Cell Line, Tumor, Fibroblasts, Humans, Hybridomas, Mice, Oncogene Proteins genetics, Protein Isoforms genetics, Protein Isoforms immunology, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism, RNA, Small Interfering, ras Proteins genetics, Antineoplastic Agents, Immunological immunology, Mutation, Oncogene Proteins immunology, ras Proteins immunology
- Abstract
There is intense interest in developing therapeutic strategies for RAS proteins, the most frequently mutated oncoprotein family in cancer. Development of effective anti-RAS therapies will be aided by the greater appreciation of RAS isoform-specific differences in signaling events that support neoplastic cell growth. However, critical issues that require resolution to facilitate the success of these efforts remain. In particular, the use of well-validated anti-RAS antibodies is essential for accurate interpretation of experimental data. We evaluated 22 commercially available anti-RAS antibodies with a set of distinct reagents and cell lines for their specificity and selectivity in recognizing the intended RAS isoforms and mutants. Reliability varied substantially. For example, we found that some pan- or isoform-selective anti-RAS antibodies did not adequately recognize their intended target or showed greater selectivity for another; some were valid for detecting G12D and G12V mutant RAS proteins in Western blotting, but none were valid for immunofluorescence or immunohistochemical analyses; and some antibodies recognized nonspecific bands in lysates from "Rasless" cells expressing the oncoprotein BRAF
V600E Using our validated antibodies, we identified RAS isoform-specific siRNAs and shRNAs. Our results may help to ensure the accurate interpretation of future RAS studies., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2017
- Full Text
- View/download PDF
132. Immunophenotypic features of dedifferentiated endometrial carcinoma - insights from BRG1/INI1-deficient tumours.
- Author
-
Hoang LN, Lee YS, Karnezis AN, Tessier-Cloutier B, Almandani N, Coatham M, Gilks CB, Soslow RA, Stewart CJ, Köbel M, and Lee CH
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Dedifferentiation, Female, Humans, Immunohistochemistry, Immunophenotyping, Middle Aged, PAX8 Transcription Factor analysis, PAX8 Transcription Factor biosynthesis, Receptors, Estrogen analysis, Receptors, Estrogen biosynthesis, Tumor Suppressor Protein p53 analysis, Tumor Suppressor Protein p53 biosynthesis, Biomarkers, Tumor analysis, Carcinoma, Endometrioid pathology, DNA Helicases deficiency, Endometrial Neoplasms pathology, Nuclear Proteins deficiency, SMARCB1 Protein deficiency, Transcription Factors deficiency
- Abstract
Aims: Dedifferentiated endometrial carcinoma (DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 (BRG1) and inactivation of SMARCB1 (INI1) were recently described as potential mechanisms underlying the histological dedifferentiation. The aim of this study was to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histological and molecular features (BRG1/INI1 deficiency)., Methods and Results: We evaluated PAX8, oestrogen receptor (ER) and p53 immunostaining in the endometrioid and the undifferentiated components of 20 BRG1/INI1-deficient DDECs and 15 BRG1/INI1-intact DDECs, and compared the results with those of 23 grade 3 endometrioid carcinomas. The differentiated endometrioid component was positive for PAX8 and/or ER in 19 of 20 BRG1/INI1-deficient DDECs, whereas the corresponding undifferentiated component of all 20 tumours showed a complete absence of PAX8 and ER staining. All except one of the BRG1/INI1-deficient tumours showed a wild-type p53 staining pattern. PAX8 and ER expression in the undifferentiated component was absent in 67% and 80% of BRG1/INI1-intact DDECs, respectively, whereas 47% of the BRG1/INI1-intact DDECs showed a mutated p53 staining pattern. In comparison, absent PAX8 expression and absent ER expression were each observed in the more solid area of 48% and 48% of grade 3 endometrioid carcinomas., Conclusions: The consistent absence of PAX8 and ER expression in molecularly defined (BRG1/INI1-deficient) DDECs suggests that the loss of PAX8 and ER expression is a fundamental feature of dedifferentiation. The frequent findings of a mutated p53 staining pattern in BRG1/INI1-intact DDECs indicate that BRG1/INI1-intact DDECs may be biologically different from BRG1/INI1-deficient tumours., (© 2016 John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
133. Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas.
- Author
-
Karnezis AN, Hoang LN, Coatham M, Ravn S, Almadani N, Tessier-Cloutier B, Irving J, Meng B, Li X, Chow C, McAlpine J, Kuo KT, Mao TL, Djordjevic B, Soslow RA, Huntsman DG, Blake Gilks C, Köbel M, and Lee CH
- Subjects
- Aged, Chromosomal Proteins, Non-Histone genetics, DNA Mutational Analysis, Endometrial Neoplasms genetics, Endometrial Neoplasms mortality, Female, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Middle Aged, Oligonucleotide Array Sequence Analysis, Tissue Array Analysis, Transcription Factors genetics, Cell Dedifferentiation physiology, Chromosomal Proteins, Non-Histone biosynthesis, Endometrial Neoplasms pathology, Transcription Factors biosynthesis
- Abstract
Dedifferentiated endometrial carcinoma is an aggressive type of endometrial cancer that contains a mix of low-grade endometrioid and undifferentiated carcinoma components. We performed targeted sequencing of eight dedifferentiated carcinomas and identified somatic frameshift/nonsense mutations in SMARCA4, a core ATPase of the switch/sucrose non-fermenting (SWI/SNF) complex, in the undifferentiated components of four tumors. Immunohistochemical analysis confirmed the loss of SMARCA4 in the undifferentiated component of these four SMARCA4-mutated cases, whereas the corresponding low-grade endometrioid component showed retained SMARCA4 expression. An expanded survey of other members of the SWI/SNF complex showed SMARCB1 loss in the undifferentiated component of two SMARCA4-intact tumors, and all SMARCA4- or SMARCB1-deficient tumors showed concomitant loss of expression of SMARCA2. We subsequently examined the expression of SMARCA2, SMARCA4, and SMARCB1 in an additional set of 22 centrally reviewed dedifferentiated carcinomas and 31 grade 3 endometrioid carcinomas. Combining the results from the index and the expansion set, 15 of 30 (50%) of the dedifferentiated carcinomas examined showed either concurrent SMARCA4 and SMARCA2 loss (37%) or concurrent SMARCB1 and SMARCA2 loss (13%) in the undifferentiated component. The loss of SMARCA4 or SMARCB1 was mutually exclusive. All 31 grade 3 endometrioid carcinomas showed intact expression of these core SWI/SNF proteins. The majority (73%) of the SMARCA4/SMARCA2-deficient and half of SMARCB1/SMARCA2-deficient undifferentiated component developed in a mismatch repair-deficient molecular context. The observed spatial association between SWI/SNF protein loss and histologic dedifferentiation suggests that inactivation of these core SWI/SNF proteins may contribute to the development of dedifferentiated endometrial carcinoma.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.