Microsatellite instability is uncommon in breast cancer

In some tumors, defects in mismatch repair enzymes lead to errors in the re plication of simple nucleotide repeat segments. This condition is commonly known as microsatellite instability (MSI) because of the frequent mutations of microsatellite sequences. Although the MSI phenotype is well recognized in some colon, gastric, pancreatic, and endometrial cancers, reports of MS I in breast cancer are inconsistent. We report here our experience with >10 ,000 amplifications of simple nucleotide repeats in noncoding genomic regio ns using DNA from 267 cases of breast cancer, including cases that represen t all major histological types of breast cancer. We rarely (10 reactions) f ound unexpected bands in amplifications of tumor DNA that were not present in amplifications of normal DNA, Moreover, repeats of these reactions did n ot confirm microsatellite instability in a single case. We also evaluated t he simple nucleotide repeats in the transforming growth factor type II rece ptor, insulin-like growth factor type II receptor, BAX, and E2F-4 genes, wh ich are frequently mutated in tumors with microsatellite instability. No mu tations of these genes were found in any of the 30 breast cancer cell lines and 61 primary breast cancer samples examined. These results indicate that mismatch repair errors characteristic of the MSI phenotype are uncommon in human breast cancer.