REGULATION AND IMPACT OF CYTOPLASMIC ARID1A IN OVARIAN CANCER

Background: ARID1A is broadly accepted to be a tumor suppressor in an increasing number of cancers, including ovarian. Silencing ARID1A in ovarian surface epithelium stimulates growth, and restoration of activity in ARID1A null ovarian and endometrial cancer cells reduces proliferation, with the latter having been verified in a xenograft murine model. Immunohistochemistry studies in ovarian clear cell carcinoma (OCCC) showed that loss of nuclear ARID1A was associated with shorter progression-free survival (PFS) and similar overall survival (OS) or with advanced stage, higher grade, suboptimal resection and nodal metastasis, though reports have been inconsistent relative to clinicopathologic associations. These prior investigations focused on nuclear localized ARID1A as a logical consequence of its tumor suppressor role in chromatin remodeling and transcriptional regulation. We recently used a well-annotated ovarian cancer tissue microarray spanning histologic subtypes to evaluate the association between ARID1A and OS (N=259). Categorization of ovarian cancers by both nuclear and cytoplasmic ARID1A staining revealed a statistically significant difference in OS between the four groups with median survival times spanning more than 5 years (p