Scientists at a Maryland-based pharmaceutical company have preliminary evidence showing that a protein in the blood may prove to be a biomarker that is more sensitive and specific than current methods of early detection for prostate cancer.
If the scientists are correct, the protein – an enzyme called human aspartyl (asparaginyl) beta-hydroxylase, or HAAH – could ultimately help reduce the number of unnecessary biopsies for prostate cancer and may identify cancer at an earlier stage when treatment would have a higher likelihood of success.
The American Cancer Society recommends that all men over 50 be screened annually with two standard tests: the prostate specific antigen, or PSA, which measures a protein in the blood; and the digital rectal exam, or DRE, which entails a physical exam of the prostate.
Yet the PSA and DRE can be inexact and, at times, not specific or sensitive to cancer. High PSA levels are found in both cancerous and healthy tissue, particularly in benign prostate disease, resulting in significant numbers of false-positive cases. The DRE, based on physician touch and skill, relies on subjective judgment. As a result, a man who has prostate cancer can have both a normal PSA and DRE. Conversely, an individual with a high PSA and an abnormal DRE could be cancer-free.
“There is a great need for a test that increases the sensitivity and specificity of those two other tests for prostate cancer,” says Stephen Keith, MD, MSPH, president and chief operating officer of Panacea Pharmaceuticals Inc.
Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.
“Currently, if an individual has a high PSA and positive DRE, the recommendation is that he has a biopsy of the prostate, and more often than not – by some estimates, as much as 80% of the time – there will not be evidence of cancer,” Keith says.
However, biopsies can be painful, expensive, and difficult to perform, and may cause a high number of infections, notes Hossein Ghanbari, PhD, CEO and chief scientific officer at Panacea.
According to Ghanbari, HAAH is overexpressed in at least 20 types of cancer tested to date, including liver, breast, ovarian, colon, esophageal, and prostate. It has been shown to be involved in tumor growth, invasiveness, and cancer spread.
The researchers previously examined tissue from more than 20 different cancer types and compared them to more than 1,000 normal tissue types. Using immunohistochemistry techniques, they found that more than 99% of cancers were positive for HAAH. None of the normal issue samples were positive.
To find a more accurate way to detect prostate cancer, Ghanbari and his co-workers at Panacea developed a test in which they could detect HAAH in blood serum.
In the current work, Ghanbari and his co-workers compared HAAH levels in the blood of 16 individuals with prostate cancer to 23 healthy individuals. Those with prostate cancer showed high HAAH levels, whereas none of the normal control individuals did.
“We’ve learned that HAAH is generally detected in prostate cancer and not in normal prostate tissue, in addition to a number of other cancers,” he says.
The scientists foresee using the HAAH test in conjunction with DRE and PSA testing. “We hope our HAAH blood test combined with PSA and DRE will increase the sensitivity and specificity of screening for prostate cancer,” Keith says. “Those without cancer can avoid unnecessary biopsies through the use of all three screening tests.”
“Having a positive DRE and high PSA, the HAAH would put the final stamp of approval,” Ghanbari says.
Panacea scientists are planning clinical trials with prostate tissue samples from 800 patients, including 400 men with prostate cancer and 400 healthy individuals.
“The goal is to be able to take someone with increasing PSA numbers and a positive DRE, measure the HAAH level, look at biopsy results, and be confident that HAAH provides the additional benefit in terms of specificity and sensitivity,” Ghanbari says. “The addition of HAAH should improve the prediction of who will have positive biopsy results for prostate cancer.”