title: Loss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell carcinoma.
abstract: Ovarian endometriosis has been associated with increased risk for ovarian clear cell carcinoma (CCC). Atypical endometriosis shares common molecular alterations with CCC and therefore, has been proposed as a precursor lesion of CCC, although it is unclear if benign endometriosis is pre-neoplastic. In this study, we examined some molecular alterations in ovarian benign endometriosis, atypical endometriosis, and CCC in comparison to papillary serous carcinoma (PSC). These included BAF250a (encoded by ARID1A), a recently identified major tumor suppressor in ovarian CCC, as well as hepatocyte nuclear factor (HNF)-1b, estrogen receptor (ER), progesterone receptor (PR), and P53. We confirmed that CCC but not PSC had loss of BAF250a expression, HNF-1b up-regulation, loss of ER expression and P53 expression. We further showed that both atypical endometriosis and adjacent CCC had loss of BAF250a expression (38.5% vs. 57.7%), HNF-1b up-regulation (53.8% vs. 92.3%), and loss of ER (84.6% vs. 92.3%) and PR (76.9% vs. 84.6%) expression. Importantly, about 20% of benign ovarian endometriosis had loss of BAF250a expression, 33% with HNF-1b up-regulation, 23% loss of ER expression and 50% loss of PR expression, respectively. The concurrent rate of loss of BAF250a expression, HNF-1b up-regulation, and loss of ER expression was not observed in any benign endometriosis, and was increased to 23.1% in atypical endometriosis, and was further increased to 42.3% in CCC. Therefore, the molecular alterations accumulate in a stepwise manner along the transformation process from benign endometriosis through atypical endometriosis to CCC. These data suggest that a portion of benign ovarian endometriosis has already undergone genetic alterations that lead to aberrant protein expression, possibly conferring a higher risk for malignant transformation.
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Xiao
authors.forename: Amad
authors.initials: A
authors.lastname: Awadallah
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051539:Hepatocyte Nuclear Factor 1-beta