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Prostate cancer aggressiveness and age: Impact of p53, BCL-2 and microvessel density
  1. Lisa Calvocoressi1,2,
  2. Edward Uchio3,
  3. John Ko1,
  4. Krishnan Radhakrishnan1,4,
  5. Mihaela Aslan1,5,
  6. John Concato1,5
  1. 1 Clinical Epidemiology Research Center, VA Connecticut Healthcare System, West Haven, Connecticut, USA
  2. 2 Yale Center for Analytic Sciences, Yale School of Public Health, New Haven, Connecticut, USA
  3. 3 Department of Urology, University of California, Irvine, Orange, California, USA
  4. 4 Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
  5. 5 Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
  1. Correspondence to Dr. John Concato, Clinical Epidemiology Research Center, West Haven, CT 06516, USA; john.concato{at}


Older men are more likely to have advanced prostate cancer at time of their diagnosis, but whether prostate tumors are inherently (biologically) more aggressive with advancing age is uncertain. To address this gap in knowledge, we analyzed data from veterans (n=971) diagnosed with prostate cancer during 1991–1995. Factors included age, detection of prostate cancer by screening, prostate-specific antigen (PSA) level, anatomic stage, and Gleason score. Information on molecular markers obtained from immunohistochemical staining of prostate tissue, included B cell lymphoma-2 (bcl-2), p53, and microvessel density (MVD), each having a previously documented association with disease progression and increased risk of prostate cancer death. We first examined the bivariate association of demographic, clinical, and molecular factors with age, and found evidence that race, screening status, Gleason score, PSA, bcl-2, p53, and MVD varied across categories of age in this study population. After further characterizing the association between age and Gleason score, we used logistic regression to examine the association between age and molecular markers—accounting for race, screening status, PSA, and Gleason score. Comparing men older than 80 years to those younger than 70 years, adjusted ORs and 95% CIs were 1.89 (0.73 to 4.92), 1.91 (1.05 to 3.46), and 2.00 (1.06 to 3.78), for positive bcl-2, p53, and MVD markers, respectively; no statistically significant associations were found for men 70–79 years old, compared with men younger than 70 years. These novel findings suggest that very elderly men often present with biologically aggressive prostate cancer; the results also have potential implications for therapeutic decision-making.

  • cancer
  • aging
  • biological markers

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  • Contributors Study concept and design: LC, EU, JC; statistical analysis: LC and JK; interpretation of the data: LC, EU, JK, KR, MA, JC; drafting the manuscript: LC, EU, JC; critical revision of the manuscript for important intellectual content: LC, EU, JK, KR, MA, JC.

  • Funding LC, JK, KR, MA and JC were supported by the Cooperative Studies Program, Department of Veterans Affairs. The funding source had no role in: the study design; the collection, analysis, and interpretation of data manuscript writing; or the decision to submit the manuscript for publication.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval VA Connecticut. Institutional review boards at the nine Veterans Affairs (VA) medical centers contributing data approved the original research protocol and waived informed consent. This analysis was approved by the Veterans Administration (VA) Healthcare System Human Studies Subcommittee and was conducted in accordance with the World Medical Association’s Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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