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Obstetrics & Gynecology 2008;111:1161-1166
© 2008 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Lynch Syndrome in Women Less Than 50 Years of Age With Endometrial Cancer

Kellie S. Matthews, MD1, Jacob M. Estes, MD1, Michael G. Conner, MD2, Upender Manne, MD2, Jenny M. Whitworth, MD1, Warner K. Huh, MD1, Ronald D. Alvarez, MD1, J. Michael Straughn, Jr, MD1, Mack N. Barnes, MD1 and Rodney P. Rocconi, MD3

From the 1Division of Gynecologic Oncology and the 2Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, Alabama; and the 3University of South Alabama, Mitchell Cancer Institute, Gynecologic Oncology, Mobile, Alabama.

OBJECTIVE: To estimate the frequency of mismatch repair deficiencies associated with hereditary nonpolyposis colorectal cancer, or Lynch syndrome, in women less than age 50 with endometrial cancer.

METHODS: Consecutive patients less than age 50 diagnosed with endometrial adenocarcinoma were identified. Available pathologic specimens were freshly sliced, and protein expression for MLH1, MSH2, MSH6, and PMS2 was evaluated by immunohistochemistry. Slides were scored on a semiquantitative method with complete absence of any of the four proteins suggesting a deficiency. All results were confirmed by microsatellite instability testing.

RESULTS: Sixty-one pathology specimens were analyzed. Twenty-one (34%) of the tumors had absence of staining of at least one of the four mismatch repair proteins determined by immunohistochemistry and confirmed by microsatellite instability testing. Obese patients were less likely than nonobese patients to have a mismatch repair deficiency (21% versus 59%, respectively). Non-obese patients had a relative risk for a mismatch repair deficiency of 5.5 (95% confidence interval 1.6–19.1; P=.01).

CONCLUSION: Many women diagnosed with endometrial cancer before age 50 will have a mismatch repair deficiency discovered by immunohistochemistry and microsatellite instability testing. A number of young women diagnosed with endometrial cancer will require further genetic testing for mismatch repair mutations.

LEVEL OF EVIDENCE: III






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