Researchers with the University of Michigan Comprehensive Cancer Center have developed a new test that could be used along with the standard PSA screenings to detect early prostate cancer and aid physicians in making treatment decisions. The Michigan Center for Translational Pathology is working with Gen-Probe Inc in hopes of offering the test to patients within the year.
An elevated prostate specific antigen (PSA) result does not always indicate prostate cancer, notes senior study author Arul Chinnaiyan, MD PhD, a professor of pathology at the U-M Medical School. “Many more men have elevated PSA than actually have cancer but it can be difficult to determine this without biopsy,” he says, which causes discomfort and some risk to the patient. “This test will help in this regard. The hope is that this test could be an intermediate step before getting a biopsy.”
Can a urine test help detect prostate cancer?
The test uses urine to detect a genetic anomaly that occurs in about half of all prostate cancers: a gene fusion involving androgen-regulated gene transmembrane protease, serine 2 (TMPRSS2) and v-ets erythroblastosis virus E26 oncogene homolog (ERG), both located on chromosome 21. In 2009, Dr. Chinnaiyan and his team identified the triggering event that leads to the two genes fusing together, causing prostate cancer to develop. Their findings, published in Science Express, suggests that stress or insult to the cells led to the gene fusion which then acts as an “on-switch” to trigger prostate cancer. Other data has suggested that TMPRSS2:ERG fusion is associated with a higher tumor stage and prostate cancer specific death.
Because TMPRSS2:ERG genetic fusion is present only half of the time, the urine test also looks for Prostate Cancer Gene 3 or PCA3. The messenger RNA of this gene is over-expressed in more than 95% of prostate cancer tissue versus normal or benign prostate tissue in the same patient.
To evaluate the reliability of the urine test, Dr. Chinnaiyan along with Scott Tomlins, MD PhD, a pathology resident at the U-M Health System, looked at samples from 1,312 men who all had elevated PSA levels and had undergone either a biopsy or a prostatectomy. The researchers stratified the patients into low, intermediate and high scores, indicating their risk of cancer and then compared this to biopsy results.
The biopsies indicated cancer in 21% of men from the low-score group, 43% from the intermediate group, and 69% in the high group. The urine test scores also correlated with how aggressive the cancer was, based on tumor size and Gleason score. The results from this clinical trial are published in the August issue of the journal Science Translational Medicine.
While the combined TMPRSS2:ERG and PCA3 test is not yet available as a prostate screening tool, the University of Michigan does offer PCA3 screening to men as a follow-up to an elevated PSA test. The test, called PROGENSATM PCA3 Assay, appears to be helpful in predicting which men have significant prostate cancer.
Read more in our Prostate Cancer Health Center.
Boormans JL et al. Expression of the androgen-regulated fusion gene TMPRSS2-ERG does not predict response to endocrine treatment in hormone-naive, node-positive prostate cancer. European Urology 2010 May; 57(5): 830-35
Mosquera JM et al. Morphological features of TMPRSS2-ERG gene fusion prostate cancer. Journal of Pathology 2007 May; 212(1): 91-101
Tomlins SC et al. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Science Translational Medicine 2011 Aug 3; 3:94ra72