The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2.
OBJECTIVE
The morphologic and molecular phenotype of breast cancers may help identify patients who are likely to carry germline mutations in BRCA1 and BRCA2. This study evaluates the immunohistochemical profiles of tumors arising in patients with mutations in these genes.


METHODS
Samples of breast cancers obtained from the International Breast Cancer Linkage Consortium were characterized morphologically and immunohistochemically using antibodies to estrogen receptor, progesterone receptor, HER-2 (c-erbB-2 oncogene), and p53 protein.


RESULTS
Breast cancers in patients with BRCA1 germline mutations are more often negative for estrogen receptor, progesterone receptor, and HER-2, and are more likely to be positive for p53 protein compared with controls. In contrast, BRCA2 tumors do not show a significant difference in the expression of any of these proteins compared with controls.


CONCLUSIONS
BRCA1 has a distinctive morphology and immunohistochemical phenotype. The combined morphologic and immunohistochemical data can be used to predict the risk of a young patient harboring a germline mutation in BRCA1. The BRCA2 phenotype is currently not well defined.
Lakhani
Sunil R
SR
Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research and the Royal Marsden Hospital, London, United Kingdom. lakhani@icr.ac.uk
Van De Vijver
Marc J
MJ
Jacquemier
Jocelyne
J
Anderson
Thomas J
TJ
Osin
Peter P
PP
McGuffog
Lesley
L
Easton
Douglas F
DF
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016009:Chi-Square Distribution; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D016015:Logistic Models; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53