BIOLOGICAL AND PROGNOSTIC-SIGNIFICANCE OF STRATIFIED EPITHELIAL CYTOKERATINS IN INFILTRATING DUCTAL BREAST CARCINOMAS

The biological significance of the differential expression of cytokera tin (CK) polypeptides in breast carcinomas is unclear. We examined the CK profiles of 101 primary infiltrating ductal breast carcinomas usin g monoclonal antibodies directed against 11 different CKs and against vimentin. Two major CK phenotypes were distinguished: first, a phenoty pe expressing only the simple-epithelial CKs 7 (variably), 8, 18 and 1 9, and secondly, a bimodal phenotype co-expressing significant amounts of one or more of the stratified-epithelial CKs 4, 14 and 17. The vas t majority of G1 and G2 carcinomas had the simple-epithelium phenotype , as did a subgroup of G3 carcinomas. Interestingly, the majority (62% ) of G3 carcinomas exhibited the bimodal phenotype, with the expressio n of CKs 4, 14 and 17 being statistically correlated with poor histolo gical differentiation and absence of steroid hormone receptors. The di stribution of vimentin only partially overlapped with that of these st ratified-epithelial CKs. Prognostic analyses suggested that the presen ce of CKs 4, 14 and/or 17 was associated with short overall and diseas e-free survival in subgroups comprising G3, oestrogen-receptor-negativ e and vimentin-negative tumours. In node-positive tumours the correlat ion between these CKs and a shorter disease-free interval attained sta tistical significance (log rank, 0.0096). Thus, abnormal CK profiles i n ductal breast carcinomas appear to reflect disturbed regulation of d ifferentiation-related gene expression programmes and may prove to be of clinical value.