Expression of basal cell keratins in human prostate cancer metastases and cell lines

Within normal human prostate epithelium, basal and luminal cells can be dis criminated by their expression of keratins (K). While basal cells express K 5/14, luminal cells show expression of K8/18 and an intermediate cell popul ation can be identified by co-expression of K5/18. Prostate cancer is predo minantly composed of luminal and neuroendocrine cells, while a minority of cells have a basal phenotype. In order to distinguish between basal and int ermediate cells and to assess, the effects of androgen deprivation on prost ate cancer, 56 human prostate cancer metastases and three cancer cell lines were characterized using antibodies to K5, K14, K18, and the neuroendocrin e marker chromogranin A (ChA). The staining was performed on paraffin tissu e and visualized by the avidin-biotin-peroxidase complex method. Protein ex pression was quantified as the number of positive cells in 20 high power fi elds (HPF; 400 x). Keratin expression in the prostate cancer cell lines LNC aP, DU145, and PC3 was analysed by immunofluorescence with triple staining and confocal laser scanning microscopy. Prostate cancer metastases were con sistently positive for K18 and negative for K14, irrespective of hormonal t herapy. K5 expression was displayed in 28.9%, of the tumours without treatm ent, in 75% after androgen deprivation, and in 57.1% of hormone-escaped pro state carcinomas. After androgen deprivation, the number of K5-expressing c ells increased significantly. While androgen-dependent prostate cancer show ed a median of 0 cells/20 HPF (range 0-50), regressed tumours displayed 22. 5 (range 0-65) and hormone-escaped tumours 7.5 (range 0-361) positive cells /20 HPF. Expression of ChA was observed in 47.4%, of the androgen-dependent tumours. The number of neuroendocrine cells was not significantly affected in regressed or hormone-escaped disease. The androgen-dependent cell line LNCaP stained for K18, while the androgen-independent lines DU145 and PC3 b oth expressed K5 and 18. Expression of K5 in the absence of K14 identifies the existence of an intermediate cell population in prostate carcinoma. Acc umulation of intermediate cells in regressed and hormone-escaped prostate c ancer indicates that for their survival, these cells are androgen-independe nt. Copyright (C) 2001 John Wiley & Sons, Ltd.