Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression

Yonsei Med J. 2017 Jan;58(1):59-66. doi: 10.3349/ymj.2017.58.1.59.

Abstract

Purpose: 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.

Materials and 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.

Conclusion: 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.

Keywords: AT rich interactive domain 1A (SWI- like), human; Adenocarcinoma, clear cell; endometriosis; estrogen receptor 2 (ER beta), human; ovarian neoplasms; prognosis.

MeSH terms

  • Adenocarcinoma, Clear Cell / metabolism*
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Clear Cell / pathology
  • Adult
  • Aged
  • Antigens, CD
  • Biomarkers, Tumor / metabolism
  • Cadherins / metabolism
  • Estrogen Receptor beta / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Transcription Factors / metabolism*

Substances

  • ARID1A protein, human
  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • Estrogen Receptor beta
  • Neoplasm Proteins
  • Nuclear Proteins
  • Transcription Factors