The Clinicopathologic Significance of p53 and BAF250a (ARID1A) Expression in Clear Cell Carcinoma of the Endometrium
Oluwole Fadare, Katja Gwin, Mohamed M Desouki, Marta A Crispens, Howard W Jones III, Dineo Khabele, Khaled Mohammed, Sharon X Liang, Wenxin Zheng, Jonathan L Hecht, Vinita Parkash. Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; UPMC, Pittsburgh, PA; North Shore-LIJ, NHP, NY; Arizona University, Tucson, AZ; Harvard University, Boston, MA; Yale University, New Haven, CT
Background: There is a dearth of information on the molecular events that underlie endometrial clear cell carcinogenesis, and validated biomarkers that are predictive of patient outcome have not been identified. Preclinical studies suggest functional interactions between the BAF250a and p53 proteins (encoded by the tumor suppressor genes ARID1A and TP53 respectively). The significance of p53 and BAF250a expression in clear cell carcinomas of the endometrium (CCC) is assessed herein.
Design: Immunohistochemical analyses for BAF250a and p53 were performed on a group of 50 CCC cases that had previously been subjected to a rigorous review process for diagnostic accuracy, and results were correlated with clinicopathologic parameters. Cases were classified as positive if ≥50% of tumor cells displayed intense immunoreactivity or if the case displayed a null phenotype.
Results: 17 (34%) of 50 cases were p53[+]; the remaining 33 cases had a p53 wild-type (p53-wt) immunophenotype. Of the 10 relapses/recurrences in the entire dataset, 80% were in the p53[+] group (p=0.003). On univariate analyses, 1) the median overall survival (OS) for the p53-wt patients (82.7 mo) was longer than the p53[+] patients (63.1 mo), a difference that approached, but did not attain statistical significance (p=0.07), 2) the median progression-free survival (PFS) for the p53[+] group (56.1 mo) was significantly lower than the p53-wt group (88.2 mo), p=0.01; 3) p53 status was not significantly associated with clinicopathologic factors, including stage distribution and morphologic patterns. On multivariate analyses, p53 expression was not associated with reduced OS or PFS. 10 of the 50 cases were BAF250a-negative, and there was no significant correlation between p53 and BAF250a expression (r = -0.03). The p53+/ BAF250a-, p53+/ BAF250a+, p53-/ BAF250a+, and p53-/ BAF250a- composite immunophenotypes were identified in 8%, 26%, 54% and 12% of cases respectively, but neither loss of BAF250a expression nor composite profiles were associated with reduced OS or PFS.
Conclusions: A significant subset of CCC express p53, and these cases are not definable by their morphologic features. p53 expression may be a negative prognostic factor, and warrants additional studies. Loss of BAF250a expression has no prognostic significance in CCC.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 116, Tuesday Morning