TRANSFORMING-GROWTH-FACTOR BETA-1 IS ASSOCIATED WITH ANGIOGENESIS, METASTASIS, AND POOR CLINICAL OUTCOME IN PROSTATE-CANCER

BACKGROUND. Prostate tumors express high levels of transforming growth factor-pi (TGF-beta 1) and seem to acquire resistance to its antiprol iferative effects with tumor progression. Moreover, TGF-beta 1 could b e involved in tumor-promoting processes such as angiogenesis, cell mig ration, and immunosuppression. METHODS. Immunoreactivity for TGF-PI an d its receptors type I and type II (TGF beta-RI and TGF beta-RII), tum or vascular count, and cell proliferation were studied in 73 cases of prostate cancer, diagnosed between 1975-1983 and followed with surveil lance. RESULTS. Patients with tumor overproduction of TGF-PI had short er median cancer-specific survival than patients with normal TGF-beta 1 immunoreactivity (5.0 vs. 10 years, P = 0.006). Furthermore, increas ed TGF-beta 1 staining was associated with tumor grade, high vascular counts, and metastasis (P = 0.02, 0.02, and 0.01, respectively). Patie nts with loss of tumor TGF beta-RII expression in combination with TGF -beta 1 overproduction showed particularly short survival (2.6 vs. 10 years, P = 0.0000), when compared to patients with normal immunoreacti vity. CONCLUSIONS. Overproduction of TGF-beta 1 and loss of TGF beta-R II expression are associated with poor clinical outcome in prostate ca ncer, and TGF-beta 1 may promote tumor progression by stimulating angi ogenesis and metastasis. Prostate 37:19-29, 1998. (C) 1998 Wiley-Liss, Inc.