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Association between Keratin and Vimentin Expression, Malignant Phenotype, and Survival in Postmenopausal Breast Cancer Patients¹

University of Iowa Cancer Center [P. A. T., D. A. K., J. R. C., R. F., E. A. S., M. J. C. H.], Departments of Pathology [P. A. T., R. F.], Ophthalmology [R. F.], Anatomy and Cell Biology [D. A. K., E. A. S., M. J. C. H.], Preventive Medicine and Environmental Health [J. R. C.], The University of Iowa, Iowa City, Iowa 52242-1109 and Health Sciences Research [T. A. S.], Mayo Clinic, Rochester, Minnesota 55905

Pathology observational reports and experimental data suggest that keratin and vimentin intermediate filament (IF) coexpression in breast cancer confers a more aggressive "interconverted" phenotype, expressing both epithelial and mesenchymal markers. In this study, we extended previous observations by measuring the expression of keratin and vimentin, in relation to other selected biomarkers of disease progression, in postmenopausal women with breast cancer. Using immunohistochemical analysis of 54 archival, formalin-fixed, paraffin-embedded invasive breast cancers from a well-defined cohort, we examined relative IF (keratin and vimentin) expression in a semiquantitative fashion and compared these results with other biological markers and survival. By univariate analysis, we found that vimentin expression was inversely associated with keratin expression alone (P = 0.0089) and directly related to histological grade (P = 0.017), nuclear grade (P = 0.027), Ki67 growth fraction (P = 0.024), and epidermal growth factor receptor immunostaining (P = 0.019). The relative expression of keratin and vimentin in approximately similar amounts characterized tumors with the poorest prognosis, as compared with keratin-high/vimentin-negative or keratin-low/vimentin-positive tumors. These latter two groups demonstrated similar Kaplan-Meier survival curves; the former group (keratin and vimentin in approximately similar amounts) demonstrated a poorer survival, with a hazard ratio of 2.1 (95% confidence interval, 0.5–9.6). These data suggest that relative keratin and vimentin IF expression is more indicative of prognosis and tumor phenotype than either IF marker detected independently.

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