Familial breast/ovarian cancer and BRCA1/2 genetic screening: the role of immunohistochemistry as an additional method in the selection of patients

J Histochem Cytochem. 2007 Nov;55(11):1105-13. doi: 10.1369/jhc.7A7209.2007. Epub 2007 Jul 11.


Only 20-25% of families screened for BRCA1/2 mutations are found positive. Because only a positive result is informative, we studied the role of BRCA1/2 immunohistochemistry as an additional method for patient selection. From 53 high-risk-affected probands, 18 (34%) had available paraffin blocks of their tumors and were selected for this study. Mutation screening was done by conformation-sensitive gel electrophoresis and multiplex ligation-dependent probe amplification. For immunohistochemistry, 21 neoplastic specimens (15 breast carcinomas, 5 ovary neoplasms, and 1 rectal adenocarcinoma) were analyzed with BRCA1 (monoclonal antibody, Ab-1, oncogene) and BRCA2 (polyclonal antibody, Ab-2, oncogene) antibodies. Absence of the BRCA1 protein was confirmed in negative tumors by Western blotting. Seven patients were positive for BRCA1/2 mutations: 5 for BRCA1 and 2 for BRCA2. Four out of five positive patients had tumors negative for BRCA1 immunostaining, and the remaining 13 BRCA1-negative patients had positive BRCA1 immunostaining in all tumor samples. Sensitivity to predict for BRCA1 mutation carriers was 80%, and specificity was 100%, with a positive predictive value of 100% and a negative predictive value of 93%. This correlation was statistically significant (p=0.001). No correlation was observed for BRCA2. If larger studies confirm these results, high-risk patients with BRCA1-negative tumors should be screened first for this gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism*
  • Breast Neoplasms / complications
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Female
  • Genetic Testing
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / complications
  • Mutation
  • Ovarian Neoplasms / complications
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Predictive Value of Tests
  • Rectal Neoplasms / complications


  • Apoptosis Regulatory Proteins
  • BLID protein, human
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human