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Microsatellite Instability and Loss of Heterozygosity in Breast Cancer¹

Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232

Microsatellite instability (MSI) has been described in colorectal and other cancers. The purpose of this study was to determine the presence of MSI in breast cancer and to correlate its occurrence with clinicopathological parameters. For microsatellite markers we examined mono-, di-, tri-, and tetranucleotide repeats that, due to their polymorphic nature, may also be used to investigate loss of heterozygosity. In 20 paired breast cancer-peripheral blood DNA samples we identified four tumors (20%) with somatic MSI. All four tumors were stage I or II, grade 1 or 2, and estrogen receptor positive. To study MSI in relation to tumor progression we also examined paired DNA samples from two ipsilateral and three contralateral breast cancers, as well as two matched tumor-metastatic lymph node specimens. None of these seven cases showed MSI, but two of the contralateral tumors revealed allelic loss of polymorphic repeats. These data suggest that MSI is an early event in mammary tumorigenesis while loss of heterozygosity may occur at a later stage.

¹ Supported in part by American Cancer Society Grant EDT-26A to F. F. P.

² To whom requests for reprints should be addressed, at Department of Pathology, TVC 4918; Vanderbilt University, Nashville, TN 37232-5310.

Received 1/ 5/94. Accepted 2/21/94.

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