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

Kazunari Sato, Junqi Qian, Jeffrey M. Slezak, Michael M. Lieber, David G. Bostwick, Erik J. Bergstralh, Robert Brian Jenkins

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1574-1580
Number of pages7
JournalJournal of the National Cancer Institute
Volume91
Issue number18
StatePublished - Sep 15 1999

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Chromosomes, Human, Pair 8
Prostate
Carcinoma
Centromere
myc Genes
Cause of Death
Prostatic Neoplasms
Multivariate Analysis
Lipoprotein Lipase
DNA Probes
Fluorescence In Situ Hybridization
Proportional Hazards Models
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sato, K., Qian, J., Slezak, J. M., Lieber, M. M., Bostwick, D. G., Bergstralh, E. J., & Jenkins, R. B. (1999). Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. Journal of the National Cancer Institute, 91(18), 1574-1580.

Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. / Sato, Kazunari; Qian, Junqi; Slezak, Jeffrey M.; Lieber, Michael M.; Bostwick, David G.; Bergstralh, Erik J.; Jenkins, Robert Brian.

In: Journal of the National Cancer Institute, Vol. 91, No. 18, 15.09.1999, p. 1574-1580.

Research output: Contribution to journalArticle

Sato, K, Qian, J, Slezak, JM, Lieber, MM, Bostwick, DG, Bergstralh, EJ & Jenkins, RB 1999, 'Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma', Journal of the National Cancer Institute, vol. 91, no. 18, pp. 1574-1580.
Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ et al. Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. Journal of the National Cancer Institute. 1999 Sep 15;91(18):1574-1580.
Sato, Kazunari ; Qian, Junqi ; Slezak, Jeffrey M. ; Lieber, Michael M. ; Bostwick, David G. ; Bergstralh, Erik J. ; Jenkins, Robert Brian. / Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. In: Journal of the National Cancer Institute. 1999 ; Vol. 91, No. 18. pp. 1574-1580.
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title = "Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma",
abstract = "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.",
author = "Kazunari Sato and Junqi Qian and Slezak, {Jeffrey M.} and Lieber, {Michael M.} and Bostwick, {David G.} and Bergstralh, {Erik J.} and Jenkins, {Robert Brian}",
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T1 - Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma

AU - Sato, Kazunari

AU - Qian, Junqi

AU - Slezak, Jeffrey M.

AU - Lieber, Michael M.

AU - Bostwick, David G.

AU - Bergstralh, Erik J.

AU - Jenkins, Robert Brian

PY - 1999/9/15

Y1 - 1999/9/15

N2 - 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.

AB - 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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