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An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non-familial breast cancers.

Authors
  • Taylor, J
  • Lymboura, M
  • Pace, P E
  • A'hern, R P
  • Desai, A J
  • Shousha, S
  • Coombes, R C
  • Ali, S
Type
Published Article
Journal
International journal of cancer. Journal international du cancer
Publication Date
Aug 21, 1998
Volume
79
Issue
4
Pages
334–342
Identifiers
PMID: 9699523
Source
Medline
License
Unknown

Abstract

The presence of BRCA1 protein was determined immunohistochemically in normal and benign breast biopsies, non-familial breast carcinomas and breast carcinomas from one or more individuals from 8 BRCA1 families. Strikingly, little staining was detected in breast carcinomas from BRCA1 families, regardless of the position or type of mutation, whereas strong immunostaining was observed in 28/28 of non-malignant breast biopsies. Furthermore, BRCA1 staining was reduced in non-familial breast carcinomas, since loss of nuclear BRCA1 staining was evident in 19% of non-familial breast carcinomas whilst a similar proportion (20%) showed absence of either cytoplasmic or nuclear BRCA1 staining. Statistical analysis indicates that breast cancer is characterised by a reduction in levels of nuclear BRCA1 in familial (p < 0.001) and non-familial breast cancer (p = 0.001). In non-familial breast cancer absence of nuclear BRCA1, but not cytoplasmic BRCA1, is more common in high grade breast carcinomas (p = 0.03) and in patients with evidence of lymph node involvement (p = 0.05). Correlation between the absence of BRCA1 protein with high grade is consistent with previous findings of a correlation between mutations in the BRCA1 gene and high grade. Our findings provide new evidence in support of BRCA1 as a tumour suppressor protein in non-familial breast cancer.

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