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Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression
Jae Yoon Choi1, Hyun Ho Han1,2, Young Tae Kim3
1Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Medical Journal
|November 23, 2016
Summary
Ovarian clear cell carcinoma (O-CCC) cases were classified by ARID1A expression. ARID1A-positive O-CCCs show distinct immunohistochemical profiles, suggesting different molecular origins compared to ARID1A-negative tumors.
Area of Science:
- Gynecologic Oncology
- Cancer Genomics
- Molecular Pathology
Background:
- Loss of AT-rich DNA-interacting domain 1A (ARID1A) is a key driver in ovarian clear cell carcinoma (O-CCC).
- O-CCC exhibits molecular and clinical behaviors intermediate between serous and endometrioid subtypes.
- Approximately half of O-CCC cases retain expression of BAF250a, the protein product of ARID1A.
Purpose of the Study:
- To identify distinct molecular signatures of ARID1A-positive O-CCC.
- To compare ARID1A-positive O-CCC with its ARID1A-negative counterpart.
- To elucidate potential differences in carcinogenesis pathways based on ARID1A expression status.
Main Methods:
- Analysis of 70 O-CCC cases.
- Evaluation of histologic grades and patterns.
- Immunohistochemistry profiling of molecular markers.
- Assessment of clinical outcomes.
Main Results:
- 69% of O-CCCs were ARID1A-negative; 31% were ARID1A-positive.
- ARID1A-positive tumors were more frequently high-grade (41% vs. 10%) and ERβ-positive (45% vs. 17%).
- ARID1A-positive tumors were less frequently HNF1β-positive (77% vs. 96%) and E-cadherin-positive (59% vs. 83%).
Conclusions:
- Ovarian clear cell carcinomas can be classified based on ARID1A expression.
- ARID1A-positive O-CCCs present unique immunohistochemical features.
- These distinct features suggest divergent molecular events in the development of O-CCC.
