title: Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression.
abstract: OBJECTIVE
  Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart.
  
  
  METHODS
  Seventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed.
  
  
  RESULTS
  Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A-positive." ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either.
  
  
  CONCLUSIONS
  We classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Han
authors.affiliation: Department of Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Baek Gil
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute (SBSI), Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute (SBSI), Yonsei University College of Medicine, Seoul, Korea. cho1988@yuhs.ac.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D004268:DNA-Binding Proteins; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C112476:ARID1A protein, human; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D004268:DNA-Binding Proteins; D047629:Estrogen Receptor beta; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: AT rich interactive domain 1A (SWI- like), human; Adenocarcinoma, clear cell; endometriosis; estrogen receptor 2 (ER beta), human; ovarian neoplasms; prognosis