Molecular markers linked with mortality risk in prostate cancer patients

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Immunohistochemical evidence of bcl-2, p53, or high microvessel density in prostate cancer biopsy specimens at diagnosis, is associated with an increased long-term risk for death from prostate cancer, according to an observational cohort study in the May 5 issue of the Annals of Internal Medicine.

John Concato, MD, at the Clinical Epidemiology Research Center at the Veterans Affairs Connecticut Healthcare System in West Haven, and colleagues sought to determine whether molecular markers of cell cycle regulation (bcl-2 and p53) and angiogenesis (?-3 integrin, vascular endothelial growth factor, and microvessel density) are associated with increased long-term risk for death among men with prostate cancer.

The researchers extracted data from medical records, including patient age, race and comorbid conditions, as well as tumor-related anatomical extent, histologic grade, prostate-specific antigen level, symptoms and treatment. Immunohistochemical analyses of tissue obtained at diagnosis, which used antibodies against the selected markers, were also conducted.

At diagnosis, the median age was 72 years, the median prostate-specific antigen level was 10.0 µg/L, and most tumors were moderately differentiated, according to the authors. During an 11- to 16-year follow-up, 71.8 percent of men died, with 21.5 percent of deaths attributable to prostate cancer.

Among 1,007 men with results for all pertinent markers and after adjustment for age and clinical characteristics, bcl-2 (adjusted hazard ratio [HR] for positive vs. negative staining, 1.61), p53 (adjusted HR for positive vs. negative staining, 1.48 and microvessel density (adjusted HR for highest vs. lowest quartile, 3.20 were associated with death from prostate cancer, the authors reported.

Acknowledging their limitations, the researchers said that their results may be affected by residual confounding. They also said that some patients were not included in complete case analyses because information was not available from clinical care records (7.5 percent) or tissue staining (12.6 percent). Concato and colleagues concluded that further studies are needed to assess whether molecular features that are associated with increased risk for death from prostate cancer are clinically useful in distinguishing patients, who might and might not benefit from particular therapies.