The histopathologic and molecular heterogeneity of
prostate cancer and the limited availability of human
tumor tissue make unraveling the mechanisms of prostate
carcinogenesis a challenging task. Our goal was to develop an ex vivo model that could be reliably used to define a prognostic signature based on gene expression profiling of cell cultures that maintained the
tumor phenotype. To this end, we derived epithelial cultures from tissue explanted from 59 patients undergoing radical
prostatectomy or cistoprostatectomy because of prostate benign
hyperplasia/
prostate cancer or bladder
carcinoma. Patient selection criteria were absence of hormonal
neoadjuvant treatment before surgery and diagnosis of clinically localized disease. Using this unique experimental material, we analyzed expression of 22,500 transcripts on the Affymetrix Human U133A GeneChip platform (Affymetrix, Inc., High Wycombe, United Kingdom). Cultures from normal/hyperplastic tissues with a prevalent
luminal phenotype and from normal prostate epithelial tissue with basal phenotype (PrEC) served as controls. We have established a large number of prostate primary cultures highly enriched in the secretory phenotype. From them, we derived an epithelial-restricted transcriptional signature that (a) differentiated normal from
tumor cells and (b) clearly separated
cancer-derived lines into two distinct groups, which correlated with indolent or aggressive clinical behavior of the disease. Our findings provide (a) a method to expand human primary prostate
carcinoma cells with a
luminal phenotype, (b) a powerful experimental model to study primary
prostate cancer biology, and (c) a novel means to characterize these
tumors from a molecular genetic standpoint for prognostic and/or predictive purposes.