Molecular markers and mortality in prostate cancer

• Published in: BJU international 2007-12, Vol.100 (6), p.1259-1263
• Main Authors: Concato, John, Jain, Dhanpat, Li, William W., Risch, Harvey A., Uchio, Edward M., Wells, Carolyn K.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; angiogenesis; bcl‐2 proto‐oncogene; Biological and medical sciences; Epidemiologic Methods; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Prognosis; Prostate-Specific Antigen - blood; prostatic neoplasms; Prostatic Neoplasms - blood; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Tumors
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2007.07136.x

OBJECTIVE To evaluate prognosis in prostate cancer by assessing the independent effect of selected molecular factors (e.g. markers of cell‐cycle regulation), in addition to the effect of traditional clinical factors (e.g. anatomical stage, histological grade), in predicting long‐term mortality among men newly diagnosed with prostate cancer. PATIENTS AND METHODS In a community‐based population of 64 545 USA veterans aged ≥ 50 years and receiving ambulatory care during 1989–90 at nine Veterans Affairs (VA) medical centres in New England, 1274 had incident prostate cancer during 1991–95. We obtained the medical records and diagnostic tissue for these men, and then extracted demographic data and clinical information, and conducted immunohistochemical assays of molecular markers in biopsy tissue, as potential prognostic factors. In this interim analysis, data on 250 patients were analysed; the main outcome was overall mortality to 31 December 2003, providing 8–13 years of follow‐up. RESULTS In 228 (91%) patients with available medical record and laboratory data, the median age was 72 years and the median prostate‐specific antigen level was 10.4 ng/mL. In adjusted (multivariate) analyses that included traditional prognostic factors, bcl‐2 staining (hazard ratio 2.14, 95% confidence interval 1.27–3.58, P = 0.004) and high microvessel density (1.76, 1.19–2.60; P = 0.005) had an independent effect on the outcome. CONCLUSIONS Bcl‐2 and microvessel density are independent predictors of subsequent death among men with prostate cancer and might have a clinical role in assisting in deciding on treatment.