Protein in prostate biopsies signals increased risk of cancer
The presence of a particular protein in biopsied prostate tissue substantially increases the likelihood that cancer will develop in that organ. This discovery is likely to help physicians to decide how closely to monitor men who are potentially at risk for prostate cancer, which is one of the most confusing and controversial dilemmas in health care.
These findings, from the Weill Cornell Medical College in New York, New York, are the first to quantify, in the setting of a clinical trial, the increased risk of prostate cancer development from the protein ERG. The trial was reported in the Journal of Clinical Oncology (2013; doi:10.1200/JCO.2013.49.8386).
Traditional means of determining risk of prostate cancer—blood tests for the protein prostate-specific antigen (PSA) and biopsies—do not always correlate well with the chances of dying from the disease. Decisions on what to do with the results of these tests can be unclear, leaving clinicians and patients frustrated and unsure of how to proceed.
The research team is looking at specific changes within prostate cells, from an initial biopsy, to determine which men have a higher risk of prostate cancer development and need repeat biopsies or other types of monitoring. This study starts to fill in the picture for about 10% of prostate biopsies.
Investigators found that 53% of men whose prostate biopsies showed expression of ERG protein developed invasive prostate cancer, compared with 35% of men whose biopsies were ERG-negative. All biopsies were classified as having high-grade prostatic intraepithelial neoplasia (HGPIN), which are lesions that may or may not morph into cancer.
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, whereas those whose HGPIN biopsies come back ERG-negative may be able to avoid unnecessary future biopsies, said the study's senior investigator, Mark Rubin, MD, of Weill Cornell.
"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," said Rubin.
"What this study shows is that not all HGPIN is equal—that is, clinically significant," Rubin added. "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."
To calculate the link between ERG and development of prostate cancer, the research team retrospectively examined prostate biopsies collected during clinical trial testing of toremifene in preventing prostate cancer. ERG protein expression was examined in HGPIN-positive biopsies from 461 enrolled men.
About 11% of participants' biopsies had ERG expression, and over time, increasing numbers of these patients developed invasive prostate cancer—about 15% within the first year of the 3-year trial, 37% within the second year, and 53% within the third year.