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

Int J Cancer. 1998 Aug 21;79(4):334-42. doi: 10.1002/(sici)1097-0215(19980821)79:4<334::aid-ijc5>;2-w.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • BRCA1 Protein / immunology
  • BRCA1 Protein / metabolism*
  • Breast / chemistry
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • COS Cells
  • Disease Progression
  • HeLa Cells
  • Humans
  • Immune Sera
  • Immunohistochemistry
  • Transfection


  • BRCA1 Protein
  • Immune Sera