Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Endometrium: Frequency and Clinicopathologic Correlation of 41 Cases
Koen K Van de Vijver, Lena Liu, Anthony J Iafrate, Esther Oliva. Massachusetts General Hospital, Boston, MA
Background: Lynch Syndrome is associated with a >40% risk of developing endometrial carcinoma, with quite variable frequency of the different histologic subtypes reported, including high-grade endometrioid carcinomas (EEC), clear cell and serous carcinomas. Recently, an increased incidence of clear cell carcinomas (CCC) of the ovary has also been described in the setting of Lynch Syndrome. However, no large series of endometrial CCC have been studied. The goals of this study are to evaluate the overall incidence of loss of DNA mismatch repair (MMR) protein expression in a series of endometrial clear cell carcinomas and its potential association with Lynch Syndrome.
Design: After IRB approval, 41 endometrial CCC were retrieved from our files from 1986 till 2010. All available H&E slides (2-12 per case) were reviewed by two gynecologic pathologists and clinicopathologic parameters were recorded. Immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was assessed.
Results: The mean age of the patients was 67.8 years (range: 40-92; 5 patients < 50). Twenty patients were diagnosed at early stage (FIGO I and II), and 21 at advanced stage (FIGO III and IV). Combined loss of MLH1 and PMS2 expression was seen in 2 patients (40 and 59 years), while combined loss of MSH2 and MSH6 expression was seen in 2 other patients (46 and 48 years). A predominant solid growth was seen in 3/4 tumors (also present in 8/37 CCC with preserved MMR proteins) and abundant peri- and intratumoral lymphoplasmacytic infiltrate in 2/4 (both with absent MSH2/MSH6) (also seen in 9/37 CCC with preserved MMR proteins). All 4 patients were diagnosed with FIGO IA tumors, and had no evidence of disease with a mean follow-up of 148 months (range: 80-220). None of these 4 patients had metachronous ovarian or colorectal carcinoma. Eleven out of the other 16 patients with early stage CCC also had no evidence of disease with a mean follow-up of 96 months (range: 6-205). Two patients with a history of colorectal carcinoma had preserved MMR protein expression and advanced stage CCC.
Conclusions: In this study, the overall frequency of DNA MMR protein abnormalities in endometrial CCC is relatively low (4/41; 9.8%) compared to a mean of 25% reported in EEC. Among patients aged ≤ 50 in our cohort, 3/5 (60%) showed loss of DNA MMR protein expression and they did not have high-stage tumors, however, clinical behavior was similar to patients without abnormal MMR protein profile, and they had not developed other evidence of Lynch Syndrome.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 178, Tuesday Morning