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Imaging, Diagnosis, Prognosis |
Authors' Affiliations: 1 The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom; 2 Molecular and Cellular Pathology, University of Queensland, Brisbane, Australia; 3 Genetic Epidemiology Unit, Cancer Research UK, Cambridge, United Kingdom; 4 Centre Jean Perrin, Clermont-Ferrand, France; 5 The Netherlands Cancer Institute, Amsterdam, the Netherlands; 6 Imperial Cancer Research Fund Genetic Epidemiology Laboratory, St. James University Hospital, Leeds, United Kingdom; 7 Department of Genetics, Dpto Genética Humana, Centro Nacional Investigaciones Oncológicas, Madrid, Spain; 8 Department of Pathology, Fundación Jiménez Díaz, Autonomous University of Madrid, Madrid, Spain; 9 Deutsches Krebsforschungszentrum, Divisions of Epidemiology and Molecular Genome Analysis, Heidelberg, Germany; 10 Department of Genetics and Pathology, Leiden University, Leiden, the Netherlands; 11 Departments of Obstetrics and Gynecology, Friedrich Alexander University, Erlangen, Germany; 12 Department of Medicine, Trinity College Medical School, St. James Hospital, Dublin, Ireland; 13 Medical Genetics, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom; 14 CRUK Cancer Genetics Group, Paterson Institute for Cancer Research, Manchester, United Kingdom; 15 Department of Medical Genetics, St. Mary's Hospital, Manchester, United Kingdom; 16 University Hospital, Nantes, France; 17 Department of Clinical Genetics and Medical Oncology, Daniel den Hoed Cancer Centre, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands; 18 Department of Molecular Biology, National Institute of Oncology, Budapest, Hungary; 19 Department of Pathology, Western Infirmary, University of Glasgow, Scotland, United Kingdom; Departments of 20 Experimental Oncology and 21 Pathology, Istituto Nazionale Tumori, Milan, Italy; 22 Max-Delbruck-Centrum fur Moleculare Medizin, Tumorgenetik, Berlin, Germany; 23 Department of Genetic Oncology and Cancer Control, Institut National de la Sante et de la Recherche Medicale EPI 9939, Paoli Calmettes Institute, Marseille, France; 24 Department of Obstetrics and Gynaecology, General Hospital, University of Vienna, Austria; 25 Sections of Cancer Genetics and Epidemiology, Institute of Cancer Research, Haddow Laboratories, United Kingdom; and 26 London School of Hygiene and Tropical Medicine, London, United Kingdom
Requests for reprints: Sunil R. Lakhani, Molecular and Cellular Pathology, School of Medicine, Mayne Medical School, University of Queensland, Herston Road, Herston, Brisbane, Queensland, Australia 4006, Australia. Phone: 61-7-3365-5340; Fax: 61-7-3365-5511; E-mail: s.lakhani{at}uq.edu.au.
Purpose: To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.
Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.
Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.
Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.
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