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Women With Synchronous Primary Cancers of the Endometrium and Ovary: Do They Have Lynch Syndrome?

From the Departments of Gynecologic Oncology, Pathology, and Clinical Cancer Genetics, the University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Karen H. Lu, MD, Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, 1155 Herman P. Pressler St, CPB 6.3244, Unit 1362, Houston, TX 77030; e-mail: khlu{at}mdanderson.org

PURPOSE: Lynch syndrome (hereditary nonpolyposis colorectal cancer; HNPCC) is an autosomal-dominant cancer predisposition syndrome that increases risk for multiple cancers, including colon, endometrial, and ovarian cancer. Revised Bethesda Criteria recommend that patients with two HNPCC-associated cancers undergo molecular evaluation to determine whether they have a mismatch repair (MMR) defect associated with HNPCC. The purpose of our study was to determine the likelihood of MMR defects (MSH2, MSH6, MLH1) in women with synchronous endometrial and ovarian cancer.

PATIENTS AND METHODS: Between 1989 and 2004, 102 women with synchronous endometrial and ovarian cancers were identified; 59 patients had tumor blocks available for analysis. Patients were divided into risk groups based on family history: high (met Amsterdam criteria), medium (personal history or first-degree relative with an HNPCC-associated cancer), and low (all others). Protein expression for MSH2, MSH6, and MLH1 was evaluated by immunohistochemistry. Microsatellite instability and MLH1 promoter methylation analyses were performed on a subset of cases.

RESULTS: Median age was 50 years. Two patients met Amsterdam criteria for HNPCC. Five additional patients, all medium-risk, had molecular findings consistent with a germline mutation of either MSH2 or MLH1. None of the low-risk patients had molecular results consistent with a germline mutation.

CONCLUSION: Overall, 7% of women in our cohort met either clinical or molecular criteria for Lynch syndrome. All of these women had a prior history or a first-degree relative with an HNPCC-associated cancer. Limiting genetic evaluation to women with synchronous endometrial and ovarian cancer who have a family history suggestive of HNPCC may appropriately identify women with Lynch syndrome.

Supported by National Institutes of Health Grant No. N01-CN-05127 (Chemoprevention of Endometrial Cancer in Hereditary Nonpolyposis Colorectal Cancer) and 1P50CA098258-01 (Specialized Program of Research Excellence in Uterine Cancer).

Presented at the Annual Meeting for The Society of Gynecologic Oncologists, Miami, FL, March 19-23, 2005.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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