Molecular Markers May Help Physicians Predict Severity of Prostate Cancer

New Haven, Conn. — In a research advance that could eventually change the way men are treated for prostate cancer, scientists at Yale University and Veterans Affairs Connecticut Healthcare System report that certain molecular markers detected in initial biopsy specimens obtained at the time of diagnosis were associated with higher death rates from the disease. The paper appears in the May 5 issue of the Annals of Internal Medicine.

A debate has been ongoing in the medical community as to whether screening and early diagnosis of prostate cancer really saves lives, or if the more relevant factor in determining survival is the severity (or “aggressiveness”) of the tumor. For many years, doctors have had few tools, such as prostate-specific antigen (PSA) tests and the so-called “Gleason score” showing the histology of the tumor, to determine severity and predict outcomes for their newly diagnosed patients. These approaches have limited the ability of patients with prostate cancer to understand how much their disease might impact their longevity.

According to the paper’s lead author, John Concato, MD, MPH, “Our results expand the current ability of clinicians to evaluate the aggressiveness of prostate cancer; future research can help to define specific biologic mechanisms and develop new therapies.”

The Yale-VA team studied tissue taken from the initial biopsies of 1,007 U.S. veterans diagnosed with prostate cancer during 1991-1995. Focusing on markers of cell cycle regulation and blood vessel formation implicated in more aggressive prostate cancer, these patients’ health status was determined through 2006.

The researchers found there was a significant statistical association between patients’ eventual death from prostate cancer and abnormal expression (using protein staining) of “bcl-2”, which regulates cell death, or of the “p53” tumor suppressor gene. Similarly, high microvessel density (the number of small blood vessels in the tumor) from biopsy specimens taken at diagnosis was also associated with an increased risk of death over 11 to 16 years.

An accompanying editorial questioned whether the results would actually change clinical practice. According to Concato, “The markers may not affect the initial treatment plan for patients who are diagnosed with prostate cancer today, but our findings can be helpful in identifying men who will not respond to current therapies and require subsequent treatment.”

Co-authors include: Dhanpat Jain, MD, Department of Pathology, Yale School of Medicine; Edward Uchio, MD, Division of Urology, Yale School of Medicine and Veterans Affairs Connecticut Healthcare System; Harvey Risch, MD, PhD, Department of Epidemiology and Public Health, Yale School of Medicine; William W. Li, MD, Angiogenesis Foundation, Cambridge, MA; and Carolyn K. Wells, MPH, of the Veterans Affairs Connecticut Healthcare System.

This research was funded by the Office of Research and Development, Veterans Health Administration.