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. To better define the clinical significance of these genetic alterations, we undertook a retrospective analysis of systemic progression and survival in patients with a single stage of prostate cancer. We ascertained all 227 patients from the Mayo Clinic Radical Prostatectomy Registry who had a histologic high-grade, pathologic stage C (pT3N0M0) tumor surgically removed between 1966 and 1987. The mean follow-up of this population of patients was 7.7 years. DNAs were extracted from cancer lesions identified in 5-micron paraffin-embedded tumor sections. Control DNAs were obtained from surgically removed lymph nodes. Paired DNA samples of 153 patients were available for analysis using 16 polymorphic microsatellite markers mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22. The frequencies of allelic imbalance for at least one marker mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22 were 30, 58, 53, and 45% of all informative cases, respectively. Allelic imbalance at 7q31 strongly correlated with systemic cancer progression and to a slightly lesser extent with cancer-specific death. Eight-year systemic cancer progression-free rates were 58 and 81% for cases with and without 7q31 allelic imbalance, respectively (P < 0.001). Eight-year prostate cancer-specific survival rates were 70 and 85% with and without 7q31 allelic imbalance, respectively (P = 0.019). Multivariate analysis indicated that allelic imbalance at 7q31 is a significant independent predictor of systemic progression (P < 0.001) and possibly prostate cancer death (P = 0.029). In addition, allelic imbalance of the specific loci D7S522 (7q31.1) and D8S258 (8p22-p21.3) was strongly associated with systemic progression (P < 0.001 and P = 0.010, respectively) and with 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 8p22-p21.3 play an important role in tumor progression, and that allelic imbalances at these regions are markers for poor prognosis in prostate carcinoma.