IMMUNOHISTOCHEMICAL ANALYSIS OF ESTRAMUSTINE BINDING-PROTEIN WITH PARTICULAR REFERENCE TO PROLIFERATIVE ACTIVITY IN HUMAN PROSTATIC-CARCINOMA

BACKGROUND. The estramustine binding protein (EMBP) specifically binds to estramustine and was first discovered in the rat ventral prostate. However, the physiological property of EMBP in the human prostate sti ll remains to be elucidated. To elucidate whether EMBP is interrelated with cellular proliferation in human prostatic carcinoma (PC), the ch ange in EMBP immunostaining during luteinizing hormone-releasing hormo ne (LH-RFI) analog administration or during Cis-platinum-based chemoth erapy, and the difference in EMBP immunostaining between hormone refra ctory (hr-PC) and untreated PC were analyzed. METHODS. Forty-six patie nts with histologically proven untreated PCs (34 were treated with LH- RH analog and 12 were treated with chemotherapy as an initial therapy) and 14 with hr-PC were used in this study. PC tissues were obtained b efore and 3 months after the initial therapy. The changes in immunosta inings for EMBP, proliferating cell nuclear antigen (PCNA), and nm23 p rotein were compared with the change in serum prostate-specific antige n (PSA) level and the histological response during the treatment. RESU LTS. The increased EMBP expression was observed in tumors with high hi stological grade and high clinical stage as well as in hr-PC. In untre ated PC, EMBP expression weakly correlated with PCNA or nm23 protein i mmunoreactivity. In PC receiving LH-RH analog, EMBP expression was sig nificantly reduced after treatment, however, no significant changes we re observed in PCNA or nm23 protein immunoreactivity. In addition, EMB P expression before the treatment significantly correlated with the se rum PSA change, while PCNA expression and nm23 protein immunoreactivit y did not. On the other hand, no significant relationship was observed between histological changes induced by the LH-RH analog and immunost ainings for EMBP, PCNA, and nm23 protein before treatment. In PC patie nts receiving chemotherapy, immunostainings for EMBP, PCNA, and nm23 p rotein were not significantly changed during the treatment. EMBP immun oreactivity was significantly higher in hr-PC than in untreated PC wit h paralleled change of PCNA expression and nm23 protein immunoreactivi ty. CONCLUSIONS. These observations indicate that EMBP is androgen reg ulated in some PCs. However, EMBP expression is demonstrated even in h r-PC and is interrelated with cellular proliferation especially in hr- PC. (C) 1997 Wiley-Liss, Inc.