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Incidence of Mismatch Repair Protein Deficiency and Associated Clinicopathologic Features in a Cohort of 104 Ovarian Endometrioid Carcinomas

Bennett, Jennifer A., MD*; Pesci, Anna, MD; Morales-Oyarvide, Vicente, MD; Da Silva, Annacarolina, MD§; Nardi, Valentina, MD; Oliva, Esther, MD

The American Journal of Surgical Pathology: February 2019 - Volume 43 - Issue 2 - p 235–243
doi: 10.1097/PAS.0000000000001165
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Patients with Lynch syndrome have up to a 24% risk of developing ovarian carcinoma, but universal mismatch repair (MMR) protein testing of ovarian carcinomas is not standard practice in most institutions. We reviewed 104 unselected ovarian endometrioid carcinomas (OEC) for various clinicopathologic features to determine if any are predictive of MMR loss. Immunohistochemistry for all 4 MMR proteins was performed followed by MLH1 promoter methylation analysis when indicated. Overall, patients had a mean age of 55 years and tumors averaged 12 cm. Most (72%) patients had stage I tumors, 63% were grade 1, and 30% had a synchronous stage IA endometrial endometrioid carcinoma. Peritumoral lymphocytes and intratumoral stromal inflammation were rare, but tumor-infiltrating lymphocytes averaged 47/10 high-power fields. Endometriosis was noted in 71%, adenofibromatous background in 14%, and both in 14% of tumors. Metaplastic changes were common and included squamous metaplasia (63%), clear cell change (32%), mucinous differentiation (24%), and sex cord-like elements (13%). When follow-up was available (n=99), 78% of patients were alive and well, 12% died from disease, 6% died from other causes, and 4% were alive with disease. Unmethylated, MMR-deficient OECs were identified in 7% of the cohort and included MSH2/MSH6 (n=4), MSH6 (n=2), and PMS2 (n=1). All these tumors were stage I, 71% grade 1, and 57% had a synchronous endometrial endometrioid carcinoma. Among patients in this group with follow-up (n=5), all were alive without evidence of disease (mean 150 mo). Given that no clinicopathologic features were associated with MMR deficiency on univariate analysis, this study highlights the importance of universal MMR screening in OECs.

*Department of Pathology and Laboratory Medicine, Lahey Hospital and Medical Center, Burlington

Department of Medical Oncology, Dana Farber Cancer Institute

§Department of Pathology, Brigham and Women’s Hospital

Department of Pathology, Massachusetts General Hospital, Boston, MA

Department of Pathology, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Jennifer A. Bennett, MD, Department of Pathology, University of Chicago Medicine, 5841 S Maryland Ave., MC 6101, Chicago, IL 60637 (e-mail: jabennett@bsd.uchicago.edu).

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