P53 MUTATIONS IN BENIGN BREAST-TISSUE

Purpose: patients with benign breast biopsies that exhibit atypical ep ithelial proliferation or fibroadenoma may be at increased risk for in vasive breast cancer. We hypothesized that molecular markers might als o be useful to evaluate the malignant potential of nonneoplastic breas t tissue. Patients and Methods: Study subjects belonged to a cohort of 6,805 women who underwent biopsy for nonmalignant breast disease at t he Mayo Clinic and Rochester-affiliated hospitals between 1967 and 198 1. As port of a nested case-control study that compared subjects who d eveloped invasive breast cancer with those who did not, we analyzed a sample of 60 benign breast biopsies for the following markers: HER-2/n eu and p53 over-expression by immunohistochemistry, HER-2/neu and PRAD -1 amplification using differential polymerase chain reaction (PCR), a nd p53 mutation using single-strand conformation analysis (SSCA) and d irect DNA sequencing by asymmetric PCR. Results: None of 60 biopsies s howed amplification of HER-2/neu or PRAD-1. Five samples exhibited low -level immunoreactivity to the HER-2/neu protein product. Fourteen sam ples exhibited focal or diffuse immunoreactivity to the p53 protein. P oint mutations in the p53 gene were found in five samples: three of th ese samples exhibited mutations that altered the amino acid sequence. Only two of five samples with p53 mutation exhibited p53 overexpressio n. Histologic diagnoses on three samples with nonconservative p53 muta tion were, respectively, nonproliferative fibrocystic change, papillom atous hyperplasia, and fibroadenoma. Conclusion: The clinical signific ance of p53 mutation, p53 overexpression, and low-level HER-2/neu expr ession in benign breast tissue remains to be determined. Further resea rch will be necessary to evaluate whether these markers could serve as useful adjuncts to histology in evaluation of the malignant potential of benign breast tissue. (C) 1995 by American Society of Clinical Onc ology.