John Concato, MD, MPH; Dhanpat Jain, MD; Edward Uchio, MD; Harvey Risch, MD, PhD; William W. Li, MD; Carolyn K. Wells, MPH
Concato J, Jain D, Uchio E, Risch H, Li WW, Wells CK. Molecular Markers and Death From Prostate Cancer. Ann Intern Med. 2009;150:595-603. doi: 10.7326/0003-4819-150-9-200905050-00005
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Published: Ann Intern Med. 2009;150(9):595-603.
Current methods to assess the prognosis of prostate cancer at the time of diagnosis are limited.
To determine whether molecular markers of cell cycle regulation (bcl-2 and p53) and angiogenesis (Î²-3 integrin, vascular endothelial growth factor, and microvessel density) are associated with increased long-term risk for death among men with prostate cancer.
Observational cohort study from 1991 to 2006.
The Veterans Affairs Healthcare System in New England.
Among 64Â 545 veterans at least 50 years of age, 1313 patients who had incident prostate cancer from 1991 to 1995 were identified. Clinical data were available for 1270 men and complete for 1172 men.
Data were extracted from medical records, including patient age, race, and comorbid conditions, as well as tumor-related anatomical extent, histologic grade (Gleason score), prostate-specific antigen level, symptoms, and treatment. Immunohistochemical analyses of tissue obtained at diagnosis, which used antibodies against the selected markers, were also conducted. Proportional hazards analysis was used to evaluate the association of these factors with death from prostate cancer through 2006.
At diagnosis, the median age was 72 years, the median prostate-specific antigen level was 10.0 Âµg/L, and most tumors were moderately differentiated. During an 11- to 16-year follow-up, 71.8% (842 of 1172) of men died, with 21.5% (181 of 842) of deaths attributable to prostate cancer. Among 1007 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 [95% CI, 1.01 to 2.57]; PÂ = 0.045), p53 (adjusted HR for positive vs. negative staining, 1.48 [CI, 1.06 to 2.08]; PÂ = 0.022), and microvessel density (adjusted HR for highest vs. lowest quartile, 3.20 [CI, 1.77 to 5.78]; PÂ < 0.001) were associated with death from prostate cancer.
Results may be affected by residual confounding. Some patients were not included in complete case analyses because information was not available from clinical care records (7.5%) or tissue staining (12.6%).
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.
Office of Research and Development, Veterans Health Administration.
Whether molecular markers distinguish indolent from aggressive prostate cancer is unclear.
This observational study of U.S. veterans found that markers of cell cycle regulation (bcl-2 and p53) and high microvessel density in biopsy specimens obtained at diagnosis were associated with increased risk for death from prostate cancer.
Some factors that might affect prognosis, such as family history, other molecular markers, and prostate-specific antigen velocity, were not assessed.
We need studies assessing 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.
Unadjusted results for bcl-2 (P < 0.001), p53 (P = 0.002), and MVD (P < 0.001) measured in quartiles of vessels per high-power microscopic field (n = 1007), excluding patients with tumors too small for staining (see text for details). hpf = high-power field; MVD = microvessel density.
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Hematology/Oncology, Prostate Cancer.
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