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.
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 patientdeath 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 patientdeath. Alterations of c-myc were associated with both systemic progression (P =.024) and patientdeath (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.
Authors: Randy S Schrecengost; Staci N Keller; Matthew J Schiewer; Karen E Knudsen; Charles D Smith Journal: Mol Cancer Res Date: 2015-08-13 Impact factor: 5.852
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Authors: J C Alers; P J Krijtenburg; A N Vis; R F Hoedemaeker; M F Wildhagen; W C Hop; T T van Der Kwast; F H Schröder; H J Tanke; H van Dekken Journal: Am J Pathol Date: 2001-02 Impact factor: 4.307
Authors: Bora Gurel; Tsuyoshi Iwata; Cheryl M Koh; Robert B Jenkins; Fusheng Lan; Chi Van Dang; Jessica L Hicks; James Morgan; Toby C Cornish; Siobhan Sutcliffe; William B Isaacs; Jun Luo; Angelo M De Marzo Journal: Mod Pathol Date: 2008-06-20 Impact factor: 7.842
Authors: Tsuyoshi Iwata; Denise Schultz; Jessica Hicks; Gretchen K Hubbard; Laura N Mutton; Tamara L Lotan; Carlise Bethel; Matthew T Lotz; Srinivasan Yegnasubramanian; William G Nelson; Chi V Dang; MengMeng Xu; Uzoma Anele; Cheryl M Koh; Charles J Bieberich; Angelo M De Marzo Journal: PLoS One Date: 2010-02-25 Impact factor: 3.240