PROGNOSTIC-SIGNIFICANCE OF ALLELIC IMBALANCE OF CHROMOSOME ARMS 7Q, 8P, 16Q, AND 18Q IN STAGE T3N0M0 PROSTATE-CANCER

Frequent allelic imbalance of polymorphic markers mapped to regions of the 7q, 8p, 16q, and 18q arms has been reported in prostate cancer. T o better define the clinical significance of these genetic alterations , we undertook a retrospective analysis of systemic progression and su rvival in patients with a single stage of prostate cancer. We ascertai ned all 227 patients from the Mayo Clinic Radical Prostatectomy Regist ry who had a histologic high-grade, pathologic stage C (pT(3)N(0)M(0)) tumor surgically removed between 1966 and 1987. The mean follow-up of this population of patients was 7.7 years. DNAs were extracted from c ancer lesions identified in 5-mu m paraffin-embedded tumor sections. C ontrol DNAs were obtained from surgically removed lymph nodes. Paired DNA samples of 153 patients were available for analysis using 16 polym orphic microsatellite markers mapped to 7q31, 8p22-p21, 16q23-qter, an d 18q21-q22. The frequencies of allelic imbalance for at least one mar ker mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22 were 30, 58, 5 3, and 45% of all informative cases, respectively. Allelic imbalance a t 7q31 strongly correlated with systemic cancer progression and to a s lightly lesser extent with cancer-specific death. Eight-year systemic cancer progression-free rates were 58 and 81% for cases with and witho ut 7q31 allelic imbalance, respectively (P < 0.001). Eight-year prosta te cancer-specific survival rates were 70 and 85% with and without 7q3 1 allelic imbalance, respectively (P = 0.019). Multivariate analysis i ndicated that allelic imbalance at 7q31 is a significant independent p redictor of systemic progression (P < 0.001) and possibly prostate can cer death (P = 0.029). In addition, allelic imbalance of the specific loci D7S522 (7q31.1) and D8S258 (8p22-p21.3) was strongly associated w ith systemic progression (P < 0.001 and P = 0.010, respectively) and w ith prostate cancer death (P < 0.001 and P = 0.009, respectively). The results suggest that a gene or genes mapped to 7q31.1 and possibly 8p 22-p21.3 play an important role in tumor progression, and that allelic imbalances at these regions are markers for poor prognosis in prostat e carcinoma. (C) 1998 Wiley-Liss, Inc.