Progression of prostate cancer to androgen independence remains the primary obstacle to improved survival. The development of more effective treatments depends on our understanding of the molecular events associated with the hormone-refractory stage. We quantified, among 90 screened genes, the expression of 37 target genes, using real-time quantitative RT-PCR. Gene expression was studied in 13 samples of HPRC compared to 33 Prostate cancer is one of the most common cancers in men and the second leading cause of cancer-related death among men in industrialised countries. 1 Androgens stimulate the growth of both normal prostate and prostate cancer, and disease progression is characterised by the transition from an androgen-dependent to an androgen-independent phenotype. Although 80% of patients with advanced prostate cancer first respond to androgen ablation therapy, within 12-18 months the tumour eventually progresses to an androgen-independent stage, resulting in poor prognosis. 2 The complex mechanisms underlying the evolution to androgen independence remain poorly understood. However, there is increasing evidence that the AR signalling pathway is associated with progression to the hormone-refractory stage, via either amplification or mutation of the AR gene. 3 Other molecular mechanisms that could be related to the multiple genetic alterations observed in advanced prostate cancer are also likely to be involved in the transition towards an androgen-independent stage, including changes in growth and apoptotic factors and neuroendocrine differentiation. Because there is no effective treatment for the hormone-refractory stage of advanced prostate cancer, understanding the mechanisms associated with the progression to androgen independence is critical to the development of new therapeutic strategies. Few studies are, however, available concerning the expression profile of advanced HRPC, probably in part because samples from hormone-resistant tumours are very rare. In the present study, we analysed by real-time quantitative RT-PCR the expression of genes involved in pathways (e.g., steroid metabolism, cell cycling, apoptosis, signal transduction, DNA repair) that are known to be dysregulated in solid tumours, including prostate carcinoma, to identify differential gene expression between normal prostate tissue, clinically localised and hormone-refractory prostate cancer.
Material and methods
Patients and tissuesClinically localised prostate tumours were obtained from 33 patients undergoing radical prostatectomy with lymph node excision and negative nodal status, including 20 cancers limited to the prostate (pT2) and 13 with extracapsular extension (pT3). Staging was assessed after pathologic examination of formalin-fixed specimens on the basis of the 1997 TNM classification. HRPC samples were obtained from 13 patients after transurethral resection. Clinical and biologic data from the 46 patients are provided (Table I). Prostatic tissue samples from 16 patients were used to assess basal levels of mRNA from target gen...
