Association between keratin and vimentin expression, malignant phenotype, and survival in postmenopausal breast cancer patients

Pathology observational reports and experimental data suggest that keratin and vimentin intermediate filament (IF) coexpression in breast cancer confe rs 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 s elected biomarkers of disease progression, in postmenopausal women with bre ast cancer, Using immunohistochemical analysis of 54 archival, formalin-fix ed, paraffin-embedded invasive breast cancers from a well-defined cohort, w e examined relative IF (keratin and vimentin) expression in a semiquantitat ive fashion and compared these results with other biological markers and su rvival. By univariate analysis, we found that vimentin expression was inver sely associated with keratin expression alone (P = 0.0089) and directly rel ated to histological grade (P = 0.017), nuclear grade (P = 0.027), Ki67 gro wth fraction (P = 0.024), and epidermal growth factor receptor immunostaini ng (P = 0.019). The relative expression of keratin and vimentin in approxim ately similar amounts characterized tumors with the poorest prognosis, as c ompared with keratin-high/vimentin-negative or keratin-lolv/vimentin-positi ve tumors. These latter two groups demonstrated similar Kaplan-Meier surviv al curves; the former group (keratin and vimentin in approximately similar amounts) demonstrated a poorer survival, with a hazard ratio of 2.1 (95% co nfidence interval, 0.5-9.6). These data suggest that relative keratin and v imentin IF expression is more indicative of prognosis and tumor phenotype t han either IF marker detected independently.