p53 mutations in benign breast tissue.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Millikan
R
R
Department of Epidemiology, University of North Carolina, Chapel Hill 27599, USA.
Hulka
B
B
Thor
A
A
Zhang
Y
Y
Edgerton
S
S
Zhang
X
X
Pei
H
H
He
M
M
Wold
L
L
Melton
L J
LJ
D001483:Base Sequence; D001706:Biopsy; D001941:Breast Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019938:Cyclin D1; D016213:Cyclins / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D018226:Fibroadenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005348:Fibrocystic Breast Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005784:Gene Amplification; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019938:Cyclin D1; D016213:Cyclins; D015513:Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53