Johns Hopkins leads the race to find better screening tests for prostate cancer.
Widespread yearly screening with the prostate-specific antigen (PSA) test has done a good job of detecting prostate cancer before it has spread. Thanks to PSA testing, many men today who are diagnosed with prostate cancer have early-stage disease that can be managed effectively with either radical prostatectomy or radiation treatment.
But the PSA test has significant limitations. The ideal screening test has a high sensitivity (it consistently identifies people who have the disease) and a high specificity (it correctly produces a negative result when a person does not have the disease). The problem with the PSA test is that PSA levels can rise for a number of reasons, including benign prostatic hyperplasia (BPH) and infection or inflammation of the prostate. As a result, more times than not, a man with an elevated PSA level does not turn out to have prostate cancer.
These so-called false-positive results are more than a false alarm or annoyance. Elevated PSA levels lead to many unnecessary and uncomfortable prostate biopsies, with some men undergoing multiple procedures. Moreover, prostate specialists continue to debate what constitutes a “normal” PSA level and the value of an isolated PSA measurement versus measuring how quickly a man’s PSA level rises over time. The PSA test is the best screening tool available, but its limitations have led to a flurry of research aimed at finding a better way to detect prostate cancer.
High hopes for EPCA as a screening test for prostate cancer
A biomarker called EPCA (for “early prostate cancer antigen”) has generated excitement in the prostate cancer community. A biomarker is a substance that can be measured in a body fluid and used to detect or monitor a disease. EPCA, which was first identified by researchers at the Brady Urological Institute at Johns Hopkins, is a protein that is present in the nucleus of prostate cancer cells. Moreover, it is rarely found in normal prostate tissue or in tissue from BPH. This characteristic distinguishes it from PSA, which can be elevated in benign conditions of the prostate.
In further research at Johns Hopkins, EPCA was identified in the seemingly normal tissue of men who went on to develop prostate cancer. This has led researchers to speculate that the protein is an indicator of early changes in cells that may eventually lead to prostate cancer. EPCA is a nuclear matrix protein, one of the proteins that forms the scaffolding that holds genetic information within the nucleus of the cell. Nuclear matrix proteins help direct the production of other critical proteins in the cell. An abnormal nuclear matrix protein, like EPCA, can alter the genetic framework of the nucleus, potentially leading to cancerous changes within the cell.
Johns Hopkins researchers have developed a test that detects EPCA in the blood. In the first clinical study of the screening test, which was reported in Cancer Research in 2005, the researchers examined blood samples from 46 men who were either healthy or had one of several health conditions. The health conditions included prostate cancer (12 patients), bladder cancer (six patients), colon cancer (two patients), kidney cancer (one patient), spinal cord injury (seven patients), and prostatitis (two patients); 16 individuals had no apparent health problems.
Eleven of the 12 men with prostate cancer were found to have high levels of EPCA in their blood, for a prostate cancer detection rate (sensitivity) of 92%. EPCA was elevated in two of the bladder cancer patients, for an overall specificity of 94%. The test did not indicate prostate cancer in any of the healthy men, for a 100% specificity in this group. A larger study is now under way, and the researchers hope that someday the EPCA test will be used along with PSA testing to reduce the number of unnecessary prostate biopsies as well as the number of prostate tumors that go undetected.
More screening tests for prostate cancer in the works
Although EPCA is the most promising prostate cancer screening test under development so far, researchers around the country are working on a variety of others. Here are just a few of the biomarkers under investigation:
- GSTP1. This protein helps prevent oxidative damage to DNA. When GSTP1 is “methylated” (inactivated by the addition of a methyl group), it suggests the presence of prostate cancer. Methylated GSTP1, which can be detected in urine, may one day help prevent repeat biopsies when a digital rectal exam indicates cancer, but the biopsy is negative.
Thymosin beta-15. This protein, which can be detected in urine, stimulates cell migration and metastasis in prostate cancer. A test for thymosin beta-15 might be combined with PSA testing to improve prostate cancer detection with fewer false-positive results.
Autoantibody signatures. A panel of 22 autoantibodies – anti-tumor proteins produced by the immune system in response to cancer -- has shown promise in detecting prostate cancer. The autoantibodies, which can be detected in blood, might one day help determine which men with elevated PSA levels need a biopsy.
With all the prostate cancer biomarker research being conducted in laboratories around the world, the PSA test may one day become just one of multiple tests routinely performed for the detection of prostate cancer.
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