Ovarian cancers arising from endometriosis: A microenvironmental biomarker study including ER, HNF1β, p53, PTEN, BAF250a, and COX-2

Background: The microenvironmental biomarkers of different subtypes of ovarian cancers arising from endometriosis have not been studied in Taiwan. Their expression can help in understanding the carcinogenic mechanism. Methods: Our study used immunohistochemistry to compare the expression of estrogen receptor (ER), hepatocyte nuclear factor-1 beta (HNF1 beta), p53, phosphatase and tensin homolog (PTEN), BAF250a, and cyclooxygenase-2 (COX-2) among 79 cases of endometriosis-associated ovarian cancers, including 40 (50%) clear cell carcinomas (CCCs), 33 (41%) endometrioid (EM) adenocarcinomas, four (5%) serous carcinomas, one adenosquamous carcinoma, and one adenosarcoma. Results: Positive stainings for ER, HNF1 beta, p53, and COX-2 were identified in 34 (43%), 30 (38%), 10 (13%), and 44 (56%) cases. Loss of PTEN and BAF250a were noted in 29 (37%) and 37 (47%) cases. The expression of ER was reversely correlated with that of HNF1 beta (rho = -0.417, p < 0.001) and correlated with p53 (rho = 0.284, p = 0.011). ER positivity was commonly identified in EM adenocarcinomas (91%), and rarely in CCCs (8%) and serous carcinoma (0%; p < 0.001). By contrast, HNF1 beta expression was frequently noted in CCCs (65%) and serous carcinomas (50%), but less in EM adenocarcinoma (6%; p < 0.001). All staining results were similar between atypical endometriosis glandular epithelium and contiguous malignant parts. Only nine cases showed 10 minor differences (10/474, 2%) in ER, HNF1 beta, and BAF250a. For the staining patterns of p53, COX-2, and PTEN, there was no difference between the invasive and precursor parts. Conclusion: Our results supported the suggestion that estrogen-dependent ovarian cancer arising from endometriosis is substantially more associated with EM adenocarcinoma than CCCs. The positive HNF1 beta staining was a frequent finding in CCCs, but not in EM adenocarcinoma. The similar staining patterns of atypical endometriosis glandular cells with the invasive parts confirmed their precursor status. Copyright (C) 2013 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.