Millions of middle-aged and older men experience the symptoms of an enlarged prostate multiple times during the day and night. What they may not know is that the disease known as BPH (benign prostatic hyperplasia), marked by urgency and frequent urination, is not one but at least a pair of disorders, and that one of the pair — tied to a newly identified gene — has far more serious implications.
In a study published in the February issue of the Journal of Urology, researchers at Johns Hopkins reported finding substantially higher levels of a protein made by a gene known as JM-27 in men whose BPH is more severe and more likely to lead to bladder-related complications if left untreated.
Although BPH affects the prostate, the resulting symptoms are often called "lower urinary tract symptoms," or LUTS. These symptoms reflect not only the direct effects of the prostate on urinary flow and urgency, but functional changes in the bladder that result from the increased pressure.
The Hopkins team, lead by Robert Getzenberg, Ph.D., also developed a blood test that detects the JM-27 protein in men with severe symptoms. The JM-27 diagnostic test, if eventually approved by the FDA, could be used to identify men with this highly symptomatic form of the disease early, before there is any damage to the bladder or urinary tract.
"Our experiments show that the expression of this marker is related to the presence of the severe form of BPH and not to the size of the prostate or to the presence or risk of prostate cancer," says Getzenberg. "What we're looking at is two diseases: BPH that produces more mild symptoms and is less likely to lead to bladder and other urinary tract damage, and BPH that is highly symptomatic with increased potential to do damage to the bladder."
In their latest study, Getzenberg and his team tested blood samples taken from 85 men. Twenty-nine had either no detectable BPH symptoms or mild ones, 39 experienced more marked symptoms of the disease, and 17 had confirmed prostate cancer.
The blood of all patients was not only screened for the presence of the JM-27 protein, but also analyzed to determine exactly how much JM-27 was in the bloodstream of each man. Researchers found a "statistically significant" difference in the levels of JM-27 in the men who were either completely asymptomatic or had mild symptoms of BPH. Men with higher levels of JM-27 had the less severe form of BPH, whereas men with low levels of JM-27 had the worse form of the disease based on their symptoms. And the presence of prostate cancer did not throw these results off; in other words, even in these men, it could be determined, based on their levels of JM-27, whether they suffered from the mild or severe form of BPH.
Getzenberg says the new biomarker test detects approximately 90 percent of the men with the severe form of BPH and only incorrectly classifies men as having this form of the disease in 23 percent of the cases.
Current medical therapy for men who suffer from BPH is with two classes of drugs: alpha blockers, which relax the prostate and 5-alpha reductase inhibitors, which help to shrink it. Forms of BPH that do not respond to medical therapies frequently require surgical intervention.
"The next step is to figure out which drugs work best on which form of the disease as differentiated by JM-27," Getzenberg says.
The incidence of BPH is estimated to equal the age of the men. Therefore, 50 percent of men in their 50s have the disease, and this increases to 80 percent for those in their 80s.