Estrogen receptor gene expression and its relation to the estrogen-inducible HSP27 heat shock protein in hormone refractory prostate cancer

BACKGROUND. The recent discovery of the classical estrogen receptor alpha ( ER alpha) in androgeninsensitive prostate cancer has shed new light on the role of estrogens in endocrine therapy failure. To get more information on downstream events of estrogen signaling in these tumors, we investigated th e relation between ER alpha gene expression, and the estrogen-inducible hea t shock protein HSP27 in recurrent prostatic adenocarcinomas. METHODS. Palliative transurethral resection specimens from 50 patients with androgen-insensitive disease were submitted for study. Messenger RNA in si tu hybridization for the ER alpha and immunohistochemistry of the HSP27 pro tein were performed on adjacent sections of an equal number of prostate can cer tissue with and without ERa protein expression. RESULTS. Cancerous lesions lacking the nuclear ER alpha at the protein leve l revealed ER alpha mRNA expression in 15 of 25 cases (60%). A coordinate e xpression of ER alpha mRNA and HSP27 was observed in 33 of 40 cases (83%), although a significant correlation between ER alpha protein and HSP27 expre ssion was not obtained. Conversely, 90% of neoplastic lesions without detec table levels of ER alpha mRNA and protein also lacked HSP27 immunoreactivit y. CONCLUSIONS. ER alpha gene expression at the mRNA level significantly corre lated with the immunoprofile of the estrogen-inducible HSP27 protein in and rogen-insensitive prostatic adenocarcinomas. This may indicate that these t umors harbor functional active estrogen receptors promoting transcriptional activity of the HSP27 gene. Determination of the receptor status by immuno histochemistry is unable to identify neoplastic lesions with established ER alpha mRNA expression in a substantial number of cases. HSP27 may be an ad ditional surrogate biomarker for estrogen-regulated growth in androgen-inse nsitive prostate cancer. (C) 2000 Wiley-Liss, Inc.