Expression of Mismatch Repair Proteins in Endocervical Adenocarcinomas: A Review of 79 Cases Including Minimal Deviation Adenocarcinomas and Problematic Lower Uterine Segment Tumors.
Anne M Mills, Sofia Liou, Christina S Kong, Teri A Longacre. Stanford University, CA
Background: Endometrial carcinoma is one of the most common malignancies seen in Lynch Syndrome (LS). Recently, the prevalence of LS has been noted to be much higher (29%) in patients with endometrial tumors localized to the lower uterine segment (LUS) when compared to the general endometrial cancer population (1.8%) (Westin et al, J Clin Oncol, 2008). In this location, distinction from endocervical primary may be difficult, particularly when atypical morphology is present, immunohistochemical stains are inconclusive, and evidence of HPV-infection is lacking. While clinical studies do not suggest an association between LS and endocervical carcinomas, mismatch repair protein (MMR) testing has not been performed in large numbers of these tumors. In this study, we examined expression of MMR proteins in endocervical adenocarcinomas and problematic LUS tumors of uncertain origin. In addition, we focused on cases of minimal deviation adenocarcinomas (adenoma malignum) which may present diagnostic difficulties due to their HPV-negative status and unconventional morphologies.
Design: Expression of MMR proteins (MSH2, MSH6, MLH1, PM2) was assessed on a tissue microarray containing 33 endocervical adenocarcinomas and 36 problematic LUS cases. The endocervical adenocarcinomas consisted of 20 invasive and 13 in situ cases. Problematic LUS cases consisted of uterine tumors for which a site of origin could not be assigned due to discordance among radiographic, gross, and morphologic findings. Representative whole slides from 10 cases of minimal deviation adenocarcinoma were also stained with all 4 MMR proteins
Results: All 33 endocervical adenocarcinomas and all 10 minimal deviation adenocarcinomas demonstrated intact expression of the 4 MMR proteins. A single problematic LUS case showed loss of MSH2 and MSH6. Although this tumor was clinically thought to represent an endocervical primary based on its location in the cervix and lower uterine segment, the tumor's immunohistochemical profile (p16 negative, vimentin negative, hormone receptor positive) was more compatible with endometrial origin.
Conclusions: Conventional endocervical adenocarcinomas and minimal deviation adenocarcinomas do not exhibit MMR protein deficiency by immunohistochemistry, indicating that these mismatch repair genes are intact in these tumors. These findings suggest that endocervical adenocarcinoma is almost certainly not a feature of LS and that loss of MMR proteins in a LUS tumor argues strongly against endocervical origin.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 216, Tuesday Morning