Progesterone receptor expression in human prostate cancer: Correlation with tumor progression

BACKGROUND. The recent discovery of the classical estrogen receptor alpha ( ER alpha) in metastatic and recurrent prostatic adenocarcinoma suggests tha t estrogens are implicated in prostate cancer progression. METHODS. To get more insight into estrogen signaling in prostate cancer tis sue, the current study has examined the immunoprofile of the estrogen-induc ible progesterone receptor (PR), and evaluated its relation to ER alpha gen e expression. RESULTS. In primary tumors, the PR was detectable in 36% of primary Gleason grade 3 (5 of 14 cases), 33% of primary Gleason grade 4 (5 of 15 cases), a nd in 58% of primary Gleason grade 5 tumors (7 of 12 cases). None of the 41 primary tumors investigated revealed significant PR expression in more tha n 50% of tumor cells. Conversely, moderate to strong receptor expression wa s observed in 60% of metastatic lesions (9 of 15 cases), and in 54% of andr ogen-insensitive tumors (38 of 71 cases). Irrespective of grades and stages , the presence of the PR was invariably associated with high steady state l evels of ER alpha mRNA, whereas the ER alpha protein was undetectable by im munohistochemistry (IHC) in a significant number of cases (58 of 97 cases). CONCLUSIONS. The progressive emergence of the PR during tumor progression o bviously reflects the ability of metastatic and androgen-insensitive tumors to use estrogens through a ER alpha -mediated pathway. The present data pr ovide a theoretical background for studying the efficiency of antiestrogens and antigestagens in the medical treatment of advanced prostate cancer. (C ) 2001 Wiley-Liss, Inc.