Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression, and ARID1A expression
Journal
Histopathology
Journal Volume
66
Journal Volume
66
Journal Issue
4
Journal Issue
4
Pages
517-528
Start Page
517
End Page
528
Date Issued
2015
Author(s)
Lin M.-C.
Huang H.-Y.
Abstract
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. ? 2014 John Wiley & Sons Ltd.
SDGs
Other Subjects
mismatch repair protein PMS2; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein MLH1; protein MSH2; protein MSH6; retinoblastoma binding protein 2; ARID1A protein, human; beta catenin; CTNNB1 protein, human; KRAS protein, human; nuclear protein; oncoprotein; phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; PIK3CA protein, human; PTEN protein, human; Ras protein; transcription factor; adult; Article; cancer growth; carcinogenesis; controlled study; CTNNB1 gene; DNA methylation; endometrioid carcinoma; endometrium carcinoma; female; gene; gene expression; gene mutation; human; human tissue; major clinical study; microsatellite instability; middle aged; mutational analysis; oncogene K ras; ovary carcinoma; phenotype; PIK3CA gene; priority journal; promoter region; protein expression; PTEN gene; real time polymerase chain reaction; young adult; endometrioid carcinoma; endometrium tumor; genetics; metabolism; mutation; ovary tumor; pathology; Adult; beta Catenin; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Microsatellite Instability; Middle Aged; Mutation; Nuclear Proteins; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins; PTEN Phosphohydrolase; ras Proteins; Transcription Factors; Young Adult
Publisher
Blackwell Publishing Ltd
Type
journal article