Prostate cancer risk raised by protein in biopsied tissue

The presence of a particular protein in biopsied prostate tissue substantially increases the likelihood that cancer will develop there, according to a recent study. 

Researchers say the discovery will likely help physicians decide how closely to monitor men potentially at risk for prostate cancer.

The findings, reported online in the Journal of Clinical Oncology (Dec. 2, 2013), are the first to quantify, in the setting of a clinical trial, the increased risk of prostate cancer development from the protein ERG.

The findings mean that potentially thousands of men each year-those with ERG-positive HGPIN biopsies-may benefit from increased surveillance and early treatment of prostate cancer, while those whose HGPIN biopsies come back ERG negative may be able to avoid unnecessary future biopsies, said senior investigator Mark Rubin, MD, of Weill Cornell Medical College, New York.

"This study is the largest ever conducted that focuses on looking at HGPIN and ERG in a systematic way. We found that more than half of patients with these biomarkers go on to develop prostate cancer, and that is a significant finding which we now want to test in a prospective clinical trial," Dr. Rubin said.

"When confirmed in larger studies, testing for ERG in these precancerous lesions may change clinical practice in how men are evaluated with abnormal biopsies and may lead to earlier cancer detection.”

The prostate cancer-specific ERG protein overproduction results from the fusion of two genes, leading to a chimeric gene referred to as TMPRSS2-ERG that is present in more than half of the 230,000 prostate cancers diagnosed in the United States each year. The fusion gene was co-discovered by Dr. Rubin in 2005.

To calculate the link between ERG and development of prostate cancer, the authors retrospectively examined prostate biopsies collected in a randomized phase III, double-blind, placebo-controlled clinical trial testing the effect of the drug toremifene (Fareston) in preventing prostate cancer. They looked for ERG protein expression in HGPIN-positive biopsies from 461 men enrolled in the clinical trial.

ERG expression was found in about 11% of participants' biopsies, and over time, increasing numbers of these patients developed invasive prostate cancer-about 15% within the first year of the 3-year trial, 37% at year two, and 53% at year three.

ERG tests from tissue and urine are already available, Dr. Rubin said, adding, "This study and other ongoing studies are beginning to shed light on the potential utility of these tests.”

Dr. Rubin is a co-inventor of the patent on the detection of gene fusions in prostate cancer, filed by the University of Michigan, Ann Arbor, and the Brigham and Women's Hospital, Boston. Several of his co-authors have a financial or other relationship with GTx, Inc., the developer of toremifene.

Licensing has been provided to Hologic Gen-Probe for diagnostic use of ETS gene fusion testing.

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