Sensitive and Specific Biomarker for Early Detection of Prostate Cancer Identified
September 13, 2006
Field(s) of Research
: Cellular and Molecular Biology, Epidemiology, Experimental and Molecular Therapeutics
CHICAGO -- 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 they’re right, 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.
Prostate cancer is expected to account for more than 234,000 new cases and about 27,000 deaths in the United States in 2006. 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 to 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,” said Stephen Keith, M.D., M.S.P.H., president and chief operating officer of Panacea Pharmaceuticals, Inc., Gaithersburg, MD.
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 percent of the time – there will not be evidence of cancer,” Dr. Keith said.
Yet, biopsies can be painful, expensive and difficult to perform, and may cause a high number of infections, noted Hossein Ghanbari, Ph.D., chief executive officer 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 percent 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 said.
The scientists foresee the HAAH test used 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,” said Keith. “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 said.
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 and look at biopsy results,” Ghanbari said, “and be confident that HAAH provides the additional benefit in terms of specificity and sensitivity. The addition of HAAH should improve the prediction of who will have positive biopsy results for prostate cancer.”
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
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