title: Familial breast/ovarian cancer and BRCA1/2 genetic screening: the role of immunohistochemistry as an additional method in the selection of patients.
abstract: 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.
authors.affiliation: Breast and Cancer Risk Evaluation Clinic, Instituto Português de Oncologia de Lisboa, Francisco Gentil, Portugal. fvaz@ipolisboa.min-saude.pt
authors.forename: Fátima H
authors.initials: FH
authors.lastname: Vaz
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Machado
authors.forename: Rita D
authors.initials: RD
authors.lastname: Brandão
authors.forename: Cátia T
authors.initials: CT
authors.lastname: Laranjeira
authors.forename: Joana S
authors.initials: JS
authors.lastname: Eugénio
authors.forename: Aires H
authors.initials: AH
authors.lastname: Fernandes
authors.forename: Saudade P
authors.initials: SP
authors.lastname: André
mesh_terms: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000150:complications; D009154:Mutation; D010051:Ovarian Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000150:complications
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human