Loss of BAF250a (ARID1A) Expression in Endometrial Clear Cell Carcinoma: Assessment of Frequency and Clinicopathologic Implications
Oluwole Fadare, Idris L Renshaw, Sharon X Liang. Vanderbilt University, Nashville; North Shore-LIJ Health System, New York
Background: SWI/SNF chromatin-modification complexes use the energy of ATP hydrolysis to remodel nucleosomes and to affect transcription in a manner that is critical for proliferation and differentiation. Accordingly, their loss of function has been associated with malignant transformation. ARID1A (the expression of whose product, BAF250a, a key complex component, is lost when mutated) has recently been identified as a tumor suppressor gene that is mutated in 50% of ovarian clear cell carcinoma (CCC). The purposes of this study are to assess the frequency of loss of BAF250a expression in endometrial CCC and whether this loss has any discernable clinicopathologic implications.
Design: 34 endometrial carcinomas with a CCC component (including 22 pure CCC, 8 mixed carcinomas with a ≥10% CCC component, and 4 carcinosarcomas with a CCC epithelial component), were evaluated by immunohistochemistry using a monoclonal antibody directed against the human BAF250a protein.
Results: 5 (22.7%) of 22 pure CCC were entirely BAF250a[-], whereas the remainder showed diffuse immunoreactivity. None of 4 carcinosarcomas and only 1 (12.5%) of 8 mixed carcinomas were BAF250a[-]. Of the 22 pts with pure CCC, 14, 2, 3, and 3 were FIGO stages 1, II, III & IV respectively. Interestingly, all 5 BAF250a[-] cases were late stage [III,IV], meaning that 83% of all late stage cases were BAF250a[-], as compared with only 1 (6.25%) of the 16 early stage cases (p=.001). 1 of 5 BAF250a[-] cases showed lymphovascular invasion, as compared with 6 of 17 BAF250a[-] cases, an insignificant difference (p>.05). As may be anticipated from the concentration of late stage cases in the BAF250a[-] group, pt outcomes were worsened, at least on univariate analysis, in that group. Pt outcomes for the pure CCC group were as follows: Alive with disease, 6 pts; No evidence of disease, NED, 11 pts; Dead of disease, DOD, 4 pts; f/u unavailable, 1 pt. 60% of the 5 BAF250a[-] pts were DOD (the other 2 were NED), as compared with only 1 (6.25%)of 16 BAF250a[+] pts (p=0.02)
Conclusions: 22.7% of endometrial CCC display complete loss of BAF250a expression. Although formal outcome analyses cannot be performed on this dataset, some noteworthy and intriguing trends did emerge, including the disproportionate concentration of BAF250a[-] cases in the late stage group and the attendant possibility of an associated worsened prognosis. These preliminary findings suggest the need for larger analyses to evaluate the prognostic significance, if any, of the loss of BAF250a expression in CCC.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 179, Tuesday Morning