Increased incidence of luteinizing hormone-releasing hormone receptor genemessenger RNA expression in hormone-refractory human prostate cancers

There are few options for treating hormone-refractory prostate cancer (PC). Various studies indicate that luteinizing hormone-releasing hormone (LHRH) agonists may have a direct inhibitory effect on prostate tumors mediated b y specific LHRH receptors. One study evaluated LHRH receptors in hormone-de pendent PC tissue, but no data have thus far been obtained on the presence of LHRH receptors in benign prostatic hyperplasia (BPH) and especially horm one-refractory PC in patients. Thus, it is not yet clear whether LHRH recep tors indicate tumor-related differentiation or even hormone-refractory dedi fferentiation or are likewise associated with BPH. The aim of this study wa s to determine the rate of LHRH receptor mRNA expression in BPH and in prim ary, potentially androgen-dependent and in hormone-refractory PC with clini cal progression. Multiplex reverse transcription-PCR was used to simultaneously detect the e xpression of mRNA for LHRH receptors and beta -actin in 48 patients with BP H, 14 with a primary, possibly hormone-dependent, prostate carcinoma (PPC), and 18 with a hormone-refractory prostate carcinoma (HRPC). Sixteen of 18 samples with HRPC showed intact RNA and expressed mRNA for LH RH receptors (100%). However. the RNA-intact PPC and BPH showed significant ly lower expression of mRNA for LHRH receptors (46.2 and 55.3%, respectivel y; variance analysis: P = 0.0017). The significantly higher expression of mRNA for LHRH receptors in HRPC indi cates that therapeutic concepts should be developed that target this site o f action. In addition to possible direct effects of LHRH agonists or antago nists demonstrated previously in vitro, it seems useful to apply targeted c ytotoxic LHRH analogues or monoclonal antibodies.