Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma

被引:172
作者
Sato, K
Qian, JQ
Slezak, JM
Lieber, MM
Bostwick, DG
Bergstralh, EJ
Jenkins, RB
机构
[1] Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Dept Urol, Rochester, MN 55905 USA
[3] Mayo Clin & Mayo Fdn, Biostat Sect, Rochester, MN 55905 USA
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 1999年 / 91卷 / 18期
关键词
D O I
10.1093/jnci/91.18.1574
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页码:1574 / 1580
页数:7
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