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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

From the Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research and the Royal Marsden Hospital, and Department of Histopathology, Royal Free and University College Medical School, London; Department of Pathology, University of Edinburgh Medical School, Edinburgh; and CRC Genetic Epidemiology Unit, Strangeways Research Laboratories, Cambridge, United Kingdom; the Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam, the Netherlands; and Department of Genetic Oncology and Cancer Control, Paoli Calmettes Institute, Marseille, France.

Address reprint requests to Sunil R. Lakhani, MD, The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, United Kingdom; email: lakhani{at}icr.ac.uk

PURPOSE: 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.

MATERIALS AND 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.

CONCLUSION: 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.

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