© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 18, 1574-1580,
September 15, 1999
© 1999 Oxford University Press
REPORTS |
Clinical Significance of Alterations of Chromosome 8 in High-Grade, Advanced, Nonmetastatic Prostate Carcinoma
Affiliations of authors: K. Sato, M. M. Lieber (Department of Urology), J. Qian, D. G. Bostwick, R. B. Jenkins (Department of Laboratory Medicine and Pathology), J. M. Slezak, E. J. Bergstralh (Section of Biostatistics), Mayo Clinic, Rochester, MN.
Correspondence to: Robert B. Jenkins, M.D., Ph.D., Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905 (e-mail: jenkins.robert{at}mayo.edu).
BACKGROUND: Chromosome 8 alterations, including loss of 8p21-22 and gain of 8q24, are commonly observed in prostate carcinoma. We examined whether these alterations are associated with poor prognosis in prostate cancer. METHODS: We used dual-probe fluorescence in situ hybridization and DNA probes for 8p22 (lipoprotein lipase gene), centromere 8 (8cen), and 8q24 (c-myc gene) to determine the corresponding copy numbers in tumor samples from 144 patients with high-grade, advanced (stage III) prostate carcinoma. Cox models were used for multivariate analysis of systemic progression or patient death from prostate cancer. All statistical tests are two-sided. RESULTS: We classified the 8p22, 8cen, and c-myc copy number as normal, loss, and gain. An additional increase (AI) category of c-myc relative to the centromere copy number (i.e., overrepresentation and amplification of c-myc) was also used. Alterations of 8p22 were not statistically significantly associated with either systemic progression or patient death. Alterations of c-myc were associated with both systemic progression (P = .024) and patient death (P = .039); AI of c-myc showed the poorest outcome. We also evaluated the prognostic relevance of the combined 8p22-8cen-c-myc loci anomaly pattern for the following six patterns: normal-normal-normal, loss-any 8cen-normal, loss-gain-gain, gain-gain-gain, non-loss-any 8cen-AI, and loss-any 8cen-AI, where any 8cen is normal, loss, or gain of the chromosome 8 centromere. Patients with the loss-any 8cen-AI pattern had earlier systemic progression (P = .009) and earlier cause-specific death (P = .013) than did patients with other patterns. Multivariate analyses demonstrated that the loss-any 8cen-AI pattern was an independent risk factor for systemic progression (P<.001) and cause-specific death (P = .002). CONCLUSIONS: Genetic alterations of chromosome 8 appear to accumulate in parallel with the progression of prostate carcinomas. AI of the c-myc gene, especially with loss of 8p22, appears to be associated with poor patient prognosis.
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