p53 Mutations in benign breast tissue

Robert Millikan, Barbara Hulka, Ann Thor, Yingchun Zhang, Susan Edgerton, Xiaoxing Zhang, Hong Pei, Mei He, Lester Wold, L. Joseph Melton, David Bollard, Kathleen Conway, Edison T. Liu

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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 non-malignant 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 overexpression 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.

Original languageEnglish (US)
Pages (from-to)2293-2300
Number of pages8
JournalJournal of Clinical Oncology
Issue number9
StatePublished - Sep 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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