Absence of genetic abnormalities in fibroadenomas of the breast determined at p53 gene mutations and microsatellite alterations.

Abstract

Genesis of breast cancer is a multistage process involving accumulation of genetic alterations, but little is known about the implication of genetic alterations in benign breast disease (BBD) lesions. Among benign lesions of the breast, one of the most common is fibroadenoma. The relationship between fibroadenoma and breast cancer is not clear. Some epidemiological studies show an association with breast cancer risk, whereas recent reports show no increased risk. In a previous study, we analyzed genetic alterations in a group of BBD lesions composed namely of fibroadenomas unaffected by breast cancer, and we found no evident implication of several loci by Southern blot method. However, genetic alterations, including p53 gene mutations, loss of heterozygosity, microsatellite instability, and cytogenetic chromosomal aberrations, have been reported recently to occur in fibroadenomas. Thus, we reexamined our BBD population for p53 gene mutations and for microsatellite alterations with 13 markers using a PCR-based method. Our results show that no molecular alterations were detected in these BBD lesions composed namely of fibroadenomas unaffected by breast cancer. Neither p53 gene mutations, determined at exons 5-9, nor microsatellite alterations tested with a very sensitive method were found in these lesions. Therefore, molecular results obtained in our study support recent epidemiological data showing that fibroadenoma does not constitute a significant increase in the relative risk of later contracting breast cancer.