title: Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression, and ARID1A expression.
abstract: OBJECTIVE
  To understand the role of and differences in molecular alterations between endometrial and ovarian endometrioid adenocarcinomas.
  
  
  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.
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
authors.forename: Hsien-Neng
authors.initials: HN
authors.lastname: Huang
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Lin
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Tseng
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Chiang
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Lin
authors.forename: Hsin-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
mesh_terms: D000328:Adult; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D014157:Transcription Factors; D051176:beta Catenin; D018631:ras Proteins; C112476:ARID1A protein, human; C495270:CTNNB1 protein, human; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C494929:PTEN protein, human
keywords: ARID1A; CTNNB1; PTEN; endometrial cancer; endometrioid adenocarcinoma; microsatellite instability; mismatch repair proteins; ovarian cancer