Journal of Clinical Oncology, Vol 13, 2293-2300, Copyright © 1995 by American Society of Clinical Oncology
p53 mutations in benign breast tissue
R Millikan, B Hulka, A Thor, Y Zhang, S Edgerton, X Zhang, H Pei, M He, L Wold and LJ Melton
Department of Epidemiology, University of North Carolina, Chapel Hill 27599, USA.
PURPOSE: Patients with benign breast biopsies that exhibit atypical
epithelial proliferation or fibroadenoma may be at increased risk for
invasive breast cancer. We hypothesized that molecular markers might also
be useful to evaluate the malignant potential of nonneoplastic breast
tissue. PATIENTS AND METHODS: Study subjects belonged to a cohort of 6,805
women who underwent biopsy for nonmalignant breast disease at the Mayo
Clinic and Rochester-affiliated hospitals between 1967 and 1981. As part of
a nested case-control study that compared subjects who developed invasive
breast cancer with those who did not, we analyzed a sample of 60 benign
breast biopsies for the following markers: HER-2/neu and p53
over-expression by immunohistochemistry, HER- 2/neu and PRAD-1
amplification using differential polymerase chain reaction (PCR), and p53
mutation using single-strand conformation analysis (SSCA) and direct DNA
sequencing by asymmetric PCR. RESULTS: None of 60 biopsies showed
amplification of HER-2/neu or PRAD-1. Five samples exhibited low-level
immunoreactivity to the HER-2/neu protein product. Fourteen samples
exhibited focal or diffuse immunoreactivity to the p53 protein. Point
mutations in the p53 gene were found in five samples: three of these
samples exhibited mutations that altered the amino acid sequence. Only two
of five samples with p53 mutation exhibited p53 overexpression. Histologic
diagnoses on three samples with nonconservative p53 mutation were,
respectively, nonproliferative fibrocystic change, papillomatous
hyperplasia, and fibroadenoma. CONCLUSION: The clinical significance of p53
mutation, p53 overexpression, and low-level HER-2/neu expression in benign
breast tissue remains to be determined. Further research 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.
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