Prevalence of DNA Mismatch Repair Protein Loss in 342 Primary Malignant Epithelial Ovarian Tumors.
Fang-I Lu, Aaron Pollett, Paul Ryan, Anne-Marie Mulligan, Blaise Clarke, Blake Gilks. Vancouver General Hospital, BC, Canada; Mount Sinai Hospital, Toronto, ON, Canada; Toronto General Hospital, ON, Canada; St. Michael's Hospital, Toronto, ON, Canada; Bon Secours Hospital, Cork, Ireland
Background: Lynch syndrome is an autosomal dominant condition caused by germline mutation in one of the DNA mismatch repair genes (hMLH1, hMSH2, hMSH6 and hPMS2), and is associated with increased risk for multiple malignancies, with colorectal carcinoma and endometrial carcinoma being the most common. Patients with Lynch syndrome are also at increased risk for ovarian malignancies, with a lifetime risk estimated at 10-12%. We analyzed the prevalence of DNA mismatch repair gene defects amongst primary malignant epithelial tumors of the ovary, using immunohistochemical staining for DNA mismatch repair (MMR) proteins.
Design: Tissue microarray (TMA) consisting of 342 primary malignant epithelial tumors of the ovary collected at Vancouver General Hospital were stained for hMLH1, hMSH2, hMSH6 and hPMS2. Positive staining for MMR proteins on TMA were verified on whole section slides for 25 randomly selected cases.
Results: Of the 342 primary malignant epithelial tumors of the ovary, loss of expression of MMR proteins was more commonly seen in the non-serous carcinomas, specifically: mucinous (1/8 cases), endometrioid (3/29 cases), clear cell (3/29 cases) and undifferentiated (1/9 cases) carcinomas, and mixed carcinomas with an endometrioid, clear cell and/or undifferentiated component (3/5 cases). The frequency of MMR protein loss was significantly higher in non-serous cases versus high-grade serous carcinomas (11/80 cases or 13.8% vs. 9/217 cases or 4.1%, p=0.007). No loss of MMR protein expression was identified in borderline tumors (22 cases), low-grade invasive serous carcinoma (9 cases) or malignant Brenner tumor (3 cases). All 25 cases positive for MMR gene products on TMA also stained positive when retested on whole section slides.
Conclusions: Our study demonstrated loss of expression of MMR proteins in 13.8% of ovarian carcinomas of non-serous types. These results raise the possibility of selective genetic screening for Lynch syndrome in patients with these types of ovarian carcinoma.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 141, Monday Morning