Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer
- 1The Gade Institute, Section for Pathology, Haukeland University Hospital, Bergen, Norway
- 2Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada
- 3Program in Cancer Genetics, McGill University, Montréal, Québec, Canada
- 4Genetic Pathology Evaluation Centre, BC Cancer Agency, UBC, Vancouver, BC, Canada
- 5Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada
- Lars A Akslen, The Gade Institute, Section for Pathology, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway; Lars.Akslen{at}gades.uib.no
- Accepted 7 July 2008
- Published Online First 4 August 2008
Abstract
Aims: BRCA1-related breast cancer is associated with a basal-like phenotype, and is frequently oestrogen receptor (ER) and HER2 negative. The expression of epidermal growth factor receptor (EGFR) has been considered to be one component of the basal-like phenotype, but no standard criteria exist. This study investigates the relationship between EGFR expression, BRCA1 status and basal markers with respect to clinicopathological associations and prognosis, in addition to evaluating different criteria for EGFR assessment by immunohistochemistry.
Methods: A tissue microarray comprising 230 available cases, from a series of primary invasive breast cancer diagnosed in Ashkenazi Jewish women during 1980–1995, was stained for EGFR using the Dako PharmDX kit, and evaluated by Webslide virtual microscopy.
Results: EGFR was positive in 9–19% according to different criteria. Expression was associated with BRCA1 carrier status and basal-like markers as negative ER, positive cytokeratin 5/6 and positive P-cadherin staining. EGFR was prognostically significant by univariate and multivariate analysis within the group carrying germ-line BRCA1 mutations. Histological grade, axillary lymph node status and P-cadherin status had significant independent value in the final multivariate model including all cases, whereas EGFR was not significant in this model. All five scoring systems gave comparable results concerning clinicopathological associations and patient outcome, although the most restrictive criteria (EGFR-HI) tended to be most sensitive in predicting BRCA1 status, a basal phenotype, and patient prognosis.
Conclusions: EGFR expression, being present in 9–19% of the cases, was prognostically significant among BRCA1 mutated cases only. In multivariate survival analysis of all cases, no independent effect was seen. However, EGFR immunostaining might be relevant to predict the response to targeted therapy, and this should be studied further.
Footnotes
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Competing interests: None.
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Ethics approval: Ethics approval was obtained from the Sir Mortimer B Davis Jewish General Hospital.
