Skip Navigation LinksHome > December 2010 - Volume 20 - Issue 9 > Microsatellite Instability and DNA Methylation of Endometria...
International Journal of Gynecological Cancer:
doi: 10.1111/IGC.0b013e3181f7b3f9
Ovarian Cancer

Microsatellite Instability and DNA Methylation of Endometrial Tumors and Clinical Features in Young Women Compared With Older Women

Zauber, N. Peter MD*; Denehy, Thad R. MD†; Taylor, Robert R. MD†; Ongcapin, Emelie H. MD‡; Marotta, Stephen P. PhD‡; Sabbath-Solitare, Marlene PhD‡; Kulkarni, Renuka MD‡; Pradhan, Tana Shah DO†; Hermelin, Daniela MD*; Bishop, D. Timothy PhD§

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Abstract

Introduction: Molecular genetic changes in endometrial cancers are important to identify possible family cancer syndromes and thus, to facilitate appropriate screening. Most studies in this regard have focused primarily on young women. We have assayed cancers for microsatellite instability (MSI) and DNA methylation from a large group of patients younger than 50 years and a comparable group of older women. We obtained personal and medical histories of the patients and their family cancer histories.

Methods: The Bethesda panel of markers was used for the detection of MSI. Methylation status of mismatch repair genes was ascertained using the methylation-specific DNA detection kit SALSA MS-MLPA No. ME011.

Results: There were 101 patients younger than 50 years and 112 older women. The 2 age groups did not differ in the percentage of patients who were obese, carried a diagnosis of diabetes, or previously had another cancer. The younger patients were more likely to be nulliparous, whereas the older patients were more likely to have hypertension. Among the younger group, 21 (20.8%) tumors revealed MSI, and 13 (61.9%) of these were unmethylated. For the older women, 35 (31.2%) had MSI tumors, and only 6 (17.1%) of these were unmethylated. Young women with a family history of a hereditary nonpolyposis colorectal cancer-related cancer were more likely to have a tumor revealing MSI and no methylation, but family history was less helpful in older women in this regard.

Conclusion: We did not find personal risk factors or a history of an additional cancer to be different between the 2 age groups. The combination of MSI testing and DNA methylation studies resulted in the identification of presumptive hereditary nonpolyposis colorectal cancer syndrome in approximately 13% of women with endometrial cancer presenting at age younger than 50 years and in approximately 5% of older women. Family history was more helpful with younger women than with older women.

Copyright © 2010 by IGCS and ESGO

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