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Int J Clin Exp Pathol 2012;5(7):642-650

Original Article
Loss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell carcinoma

Wenbin Xiao, Amad Awadallah, Wei Xin

Department of Pathology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106, USA;
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA

Received July 5, 2012; Accepted August 3, 2012; Epub September 5, 2012; Published September 15, 2012

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. (IJCEP1207004).

Keywords: ARID1A/BAF250a, endometriosis, clear cell carcinoma, papillary serous carcinoma, hepatocyte nuclear factor-1b, atypical
endometriosis, ovarian carcinoma

Address all correspondence to:
Wei Xin, MD, PhD
Department of Pathology
Case Western Reserve University
2103 Cornell Rd, Cleveland, OH 44106, USA.
Tel: 216-844-4976.
E-mail: wei.xin@case.edu