Loss of heterozygosity and microsatellite instability in epithelial hyperplasia of the breast.

We evaluated loss of heterozygosity (LOH) and microsatellite instability (MSI) in epithelial hyperplasia of the breast by the PCR method using microsatellite markers. Seven loci of 16q, 17p, 17q, and 18q were examined in 35 lesions of epithelial hyperplasia observed in non-neoplastic breast tissue of eight breast carcinoma cases, and 29 lesions were observed within 19 fibroadenomas. These hyperplastic lesions were classified by standard criteria into three groups, namely, mild, moderate and atypical ductal hyperplasia (ADH). In the breast carcinoma cases, the frequency of loss of heterozygosity was 40% in mild, 50% in moderate, and 100% in ADH; while in the fibroadenoma cases, the frequency was 10% in mild, 27% in moderate, and 25% in ADH; total frequency of LOH was statistically higher in carcinoma cases than in fibroadenoma cases. On the other hand, the frequency of microsatellite instability was higher in fibroadenoma cases (28%) than in breast carcinoma cases (11%). Furthermore, we analyzed two cases of noninvasive ductal carcinoma arising in fibroadenoma, which had various types of hyperplasia along with carcinoma in situ, and many hyperplasias showed LOH at several of the same markers as carcinoma in situ. From those results, we speculated that LOH at these markers is an early event in mammary tumorigenesis, and some of the hyperplastic lesions with LOH have precancerous natures.