Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression, and ARID1A expression

• Published in: Histopathology Vol. 66; no. 4; pp. 517 - 528
• Main Authors: Huang, Hsien-Neng, Lin, Ming-Chieh, Tseng, Li-Hui, Chiang, Ying-Cheng, Lin, Liang-In, Lin, Yu-Feng, Huang, Hsin-Ying, Kuo, Kuan-Ting
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2015; Wiley Subscription Services, Inc
• Subjects: Adult; ARID1A; beta Catenin - genetics; beta Catenin - metabolism; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - metabolism; Carcinoma, Endometrioid - pathology; Class I Phosphatidylinositol 3-Kinases; CTNNB1; endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; endometrioid adenocarcinoma; Female; Humans; Microsatellite Instability; Middle Aged; mismatch repair proteins; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins p21(ras); PTEN; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; ras Proteins - genetics; ras Proteins - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Young Adult; mismatch repair proteins; microsatellite instability; ovarian cancer; endometrioid adenocarcinoma; PTEN; endometrial cancer; CTNNB1; ARID1A
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.12543

Aims To understand the role of and differences in molecular alterations between endometrial and ovarian endometrioid adenocarcinomas. Methods and results We investigated the microsatellite status of 26 ovarian endometrioid adenocarcinomas (OVEMs), 42 endometrial endometrioid adenocarcinomas (EMCAs), and 19 concurrent (endometrial and ovarian) endometrioid adenocarcinomas. We evaluated the expression of the mismatch repair proteins, PTEN and ARID1A, and mutations of PTEN, KRAS, CTNNB1, and PIK3CA. High levels of microsatellite instability (MSI‐H) were present in one of 26 OVEMs, 12 of 42 EMCAs, and four of 19 concurrent endometrioid adenocarcinomas. Only four of 19 concurrent endometrioid adenocarcinomas showed identical molecular alterations in their endometrial and ovarian components. Loss of ARID1A or loss of PTEN expression, and MSI‐H, were more common in EMCAs than OVEMs (P = 0.044, P = 0.004, and P = 0.012, respectively). MSI‐H in endometrial endometrioid adenocarcinomas was also related to loss of ARID1A expression (P < 0.001). In the cohort of MSI‐H endometrioid adenocarcinomas involving the endometrium (n = 16), MSH6‐deficient cases showed higher frequencies of CTNNB1 and PIK3CA mutations (P = 0.008 and P = 0.036, respectively), but lower frequencies of KRAS mutation (P = 0.011), than PMS2‐deficient cases. Conclusions The different frequencies of molecular genetic alterations between endometrial endometrioid adenocarcinomas and ovarian endometrioid adenocarcinomas imply that distinct processes may be involved in their tumorigenesis or tumour progression.