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 (for 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."
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 Johns Hopkins team, led by Robert Getzenberg, 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," Getzenberg said. "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; 29 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 incorrectly classifies men as having this form of
the disease in only 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 said.
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 the incidence increases to 80 percent for
those in their 80s.
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