Loss of ARID1A-Associated Protein Expression is a Frequent Event in Clear Cell and Endometrioid Ovarian Cancers

Abstract

Background Inactivating somatic mutations in the ARID1A gene are described in a significant fraction of clear cell and endometrioid ovarian cancers leading to loss of the corresponding protein (BAF250a). Expression of BAF250a was examined in clear cell and endometrioid cancers accrued as part of the North Carolina Ovarian Cancer Study, a population-based case-control study, to determine whether loss of expression is associated with clinical and epidemiological features. Methods Immunostaining for BAF250a was performed using 212 clear cell and endometrioid ovarian cancers. Associations between loss of BAF250a and clinical and epidemiological features were examined. Variables were analyzed by logistic regression. Results Loss of BAF250a expression was noted in 96 (45%) of 212 cancers: 34(41%) of 82 clear cell cases and 62 (48%) of 130 endometrioid cases. There was no relationship between the loss of BAF250a and stage, grade, survival, or epidemiological variables. Conclusions These data confirm that loss of the ARID1A-encoded protein BAF250a is a frequent event in the genesis of clear cell and endometrioid ovarian cancers. Loss of BAF250a was not associated with clinical or epidemiologic characteristics. One explanation for these findings is that inactivation of the chromatin remodeling pathway may be a requisite event in the development of these cancers.

Clinicopathologic analysis of loss of AT-rich interactive domain 1A expression in endometrial cancer

“…The present results suggest that ARID1A expression is not significantly related to those factors. This finding is similar to previous reports analyzing the clinicopathologic relationship of ARID1A expression in cervical carcinoma [23] and OCCC [24,25]. In contrast to these reports, Fadare et al [16] showed that loss of ARID1A expression seems to be a negative prognostic factor in endometrial clear cell carcinomas.…”

New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation Sequencing

“…ARID1A is believed to function as a tumor suppressor [40]. ARID1A mutations have been reported in endometrial cancer (50%, 2 of 4), head and neck squamous cell carcinoma (50%, 3 of 6), ovarian cancer (34%, 97 of 282), skin squamous and basal cell carcinoma (29%, 2 of 7), gastric cancer (11%, 11 of 101), colorectal cancer (9%, 12 of 131), prostate cancer (9%, 2 of 23), pancreatic cancer (8%, 15 of 178), and a small percentage of lung, breast, and kidney carcinomas and gliomas (as shown in the COSMIC database in April 2012) [41]. Mutations span the length of the ARID1A gene and include point mutations and small deletions and insertions.There are no reports of ARID1A mutation in cholangiocarcinoma (as shown in the COSMIC database in April 2012), and there are no reports of ARID1A mutation in cholangiocarcinoma in the literature.…”

The emerging roles of ARID1A in tumor suppression

“…In ovarian clear cell carcinoma, no significant differences in survival between ARID1A-negative and ARID1A-positive cases were observed in four different studies. 25,27,28,37 In endometrial cancer, no association between ARID1A loss and disease-specific survival was observed in three studies on endometrioid carcinoma, 34,35,88 or in one study on clear cell carcinoma. 37 In cervical cancer, ARID1A loss was a predictor of reduced overall survival in one study, 39 but not in another.…”