Title

Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype-specific Lynch syndrome screening in ovarian carcinomas

Document Type

Article

Department

Obstetrics and Gynaecology (East Africa)

Abstract

Aims: Lynch syndrome screening in ovarian carcinoma is controversial. This study aims to assess the frequency of deficient mismatch repair protein (dMMR) in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types.

Methods and Results: Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas but none in other histological types. Within endometrioid carcinomas, 11/25 dMMR cases showed abnormal MLH1/PMS2, 10 cases abnormal MSH2/MSH6 and 4 cases isolated abnormal MSH6 indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three and isolated abnormal MSH6 in one case all probably related to Lynch syndrome. Within endometrioid carcinomas dMMR was significantly associated with age under 50 years, synchronous endometrial endometrioid carcinoma, higher CA125 level at diagnosis, higher FIGO grade, absence of ARID1A and at least 20 CD8 positive intraepithelial lymphocytes per high power field but was not associated with cancer specific death. Age under 50, higher CA125 levels at diagnosis and at least 20 CD8 positive intraepithelial lymphocytes per high power field remained significant after adjusting for multiple testing but their sensitivity to identify dMMR remained insufficient.

Conclusion: Our data support the motion for a histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas. This article is protected by copyright. All rights reserved.

Publication

Histopathology