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Clinical Cancer Research Vol. 6, 2417-2423, June 2000
© 2000 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Immunohistochemical Analyses of Focal Adhesion Kinase Expression in Benign and Malignant Human Breast and Colon Tissues: Correlation with Preinvasive and Invasive Phenotypes1

William G. Cance2, Janet E. Harris, Mary V. Iacocca, Elizabeth Roche, XiHui Yang, Jinli Chang, Stephen Simkins and LiHui Xu

Departments of Surgery [W. G. C., J. E. H., E. R., X. Y., J. C., L. X.] and Pathology [M. V. I.] and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599-7210, and Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27695 [S. S.]

The focal adhesion kinase (FAK) is a protein tyrosine kinase linked to signaling events between cells and the extracellular matrix. Studies at the Western blot level have demonstrated up-regulation of FAK expression in invasive breast and colon cancers. To assess p125FAK expression at the cellular level, we developed monoclonal antibodies that specifically detected FAK in formalin-fixed, paraffin-embedded tissue sections and analyzed the levels of FAK expression in human breast and colon tissues. Monoclonal antibody 4.47 demonstrated FAK-specific focal adhesion staining by immunofluorescence assays on BT-474 breast cancer cells and detected a Mr 125,000 protein by both Western blotting and immunoprecipitation analyses. Using immunohistochemical techniques, the expression of p125FAK was analyzed in 36 normal and 43 preinvasive or invasive human breast and colon tissues from individual patients. FAK was weakly expressed in most benign breast epithelium but was up-regulated at moderate or strong levels in 14 of 18 invasive breast carcinomas. In seven samples of ductal carcinoma-in situ, FAK was overexpressed. Borderline-to-weak expression of FAK was detected in the normal colonic epithelium. In the invasive colon cancers, FAK was overexpressed at moderate or strong levels in 13 of 15 tumors. Furthermore, FAK expression was up-regulated in areas of dysplastic, premalignant colon epithelium. These results provide the first evidence at the cellular level that FAK expression is variably overexpressed in breast and colon cancer and suggest that up-regulation occurs at an early stage of tumorigenesis.




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