title: Ovarian cancers arising from endometriosis: a microenvironmental biomarker study including ER, HNF1ß, p53, PTEN, BAF250a, and COX-2.
abstract: 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 (HNF1ß), 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, HNF1ß, 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 HNF1ß (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, HNF1ß 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, HNF1ß, and BAF250a. For the staining patterns of p53, COX-2, and PTEN, there was no difference between the invasive and precursor parts.
  
  
  CONCLUSIONS
  Our results supported the suggestion that estrogen-dependent ovarian cancer arising from endometriosis is substantially more associated with EM adenocarcinoma than CCCs. The positive HNF1ß 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.
authors: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department of Pathology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: crlai@vghtpe.gov.tw.
authors: Chiung-Ru
authors: CR
authors: Lai
authors: Chih-Yi
authors: CY
authors: Hsu
authors: Yi-Jen
authors: YJ
authors: Chen
authors: Ming-Shyen
authors: MS
authors: Yen
authors: Kuan-Chong
authors: KC
authors: Chao
authors: Anna Fen-Yau
authors: AF
authors: Li
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry; D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000032:analysis; D004268:DNA-Binding Proteins; D004715:Endometriosis / Q000150:complications* / Q000473:pathology; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000032:analysis; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry; D009687:Nuclear Proteins / Q000032:analysis; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000209:etiology / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D059016:Tumor Microenvironment / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051539:Hepatocyte Nuclear Factor 1-beta; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: biomarkers; endometriosis; ovarian neoplasms