Originally published as JCO Early Release 10.1200/JCO.2005.04.1574 on March 20 2006

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Clinicopathologic Significance of Defective DNA Mismatch Repair in Endometrial Carcinoma

Destin Black, Robert A. Soslow, Douglas A. Levine, Carmen Tornos, Shirley C. Chen, Amanda J. Hummer, Faina Bogomolniy, Narciso Olvera, Richard R. Barakat, Jeff Boyd

From the Departments of Surgery, Pathology, Epidemiology and Biostatistics, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Jeff Boyd, PhD, Department of Surgery, Box 201, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: boydj{at}mskcc.org

PURPOSE: Defective DNA mismatch repair is commonly present in sporadic manifestations of gastrointestinal, endometrial, and other cancers. The pathognomonic molecular manifestation of this repair defect is microsatellite instability (MSI). Here, we test the hypothesis that MSI predicts the clinicopathologic features of endometrial carcinoma.

PATIENTS AND METHODS: A retrospective cohort of 473 patients treated for endometrial carcinoma at this institution was identified. All cases were reviewed by a gynecologic pathologist, and clinical information was abstracted from medical records. Using consensus criteria, DNA samples from nontumor and tumor tissue pairs were genotyped for MSI. Associations between MSI status and pathologic and clinical variables were assessed.

RESULTS: Ninety-three (20%) of 473 tumors were MSI+. In the MSI+ tumor group compared with the MSI– tumor group, the proportion of advanced compared with early-stage tumors was higher (92% v 81%; P = .01), as was the proportion of tumors of endometrioid compared with nonendometrioid histologic subtype (94% v 23%; P = .001), and the proportion of tumors with myometrial invasion compared with those with none (92% v 78%; P = .01). By multivariate analyses, disease-free survival (hazard ratio, 0.3; 95% CI, 0.2 to 0.7) and disease-specific survival (hazard ratio, 0.3; 95% CI, 0.1 to 0.8) were significantly improved in patients with MSI+ tumors.

CONCLUSION: In endometrial carcinoma, the presence of MSI was independently associated with a more favorable clinical outcome.

Supported by Grant No. R01 CA100272 from the National Institutes of Health, Bethesda, MD.

Presented at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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