New Prostate Cancer Test May Identify Aggressive Form of the Disease

August 8, 2011

Scientists at the Center for Translational Pathology and the department of urology at the University of Michigan Medical School have developed a new noninvasive urine test for prostate cancer that may be able to stratify patients by risk.

Scientists at the Center for Translational Pathology and the department of urology at the University of Michigan Medical School have developed a new noninvasive urine test for prostate cancer that may be able to stratify patients by risk. The results of the study and test description are published in the August 3 edition of Science Translational Medicine.[1]


3D surface model of prostate-specific antigen (PSA)

Currently, more than 1 million men in the U.S. have an annual prostate biopsy. Most of these biopsies are performed because of an elevated serum PSA. The PSA test is FDA-approved and performed in conjunction with a digital rectal exam in order to detect prostate cancer in men 50 and over who may be asymptomatic.

"The PSA test is just that-it's very specific for prostate tissue, but it's not specific for prostate cancer,” says Scott Tomplins of the University of Michigan and first author of the study. 

Many unnecessary biopsies are conducted in men with elevated PSA levels because the elevation of this biomarker can also be a sign of benign prostate conditions such as an enlarged prostate.

Arul M. Chinnaiyan and colleages sought to develop a new read-out for prostate cancer due to the non-specificity and unclear mortality benefit of PSA testing. The goal was to find a novel biomarker or biomarkers that can facilitate the individualization of PSA levels. 

The test the researchers developed is a clinical-grade, transcription-mediated amplification assay that can detect prostate cancer non-invasively in the urine. The read-out of the test is the quantitative measure of a TMPRSS2:ERG fusion transcript that is unique to prostate cancer. More than 50% of PSA-screen prostate cancer harbors this fusion between the transmembrane protease, serine 2 (TMPRSS2) and the v-ets erythroblastosis virus E26 oncogene homolog (avian) (EGR) gene.

“It puts two genes together-TMPRSS2 and ERG-that sort of function as an 'on' switch in the prostate, that's what TMPRSS2 does, and then ERG is a gene that causes cells to become cancerous. And so you basically turned on a bad gene in the prostate," says Tomplins.

In the prospective study, 1312 men were screened and the analysis found that this fusion transcript was associated with indicators of clinically significant cancer at biopsy and prostatectomy, including tumor size and high Gleason score at prostatectomy. All of the men had elevated PSA levels and were referred to undergo a needle biopsy.

This test in combination with detection of urine prostate cancer antigen 3 (PCA3) improved the performance of the multivariate Prostate Cancer Prevention Trial risk calculator in predicting cancer on biopsy. The men with the highest and lowest TMPRSS2:ERG+PCA3 had very different rates of cancer, clinically significant caner, and high-grade cancer detected by biopsy. 

While the test can help doctors make a more educated decision about further testing and biopsy for men with elevated PSA levels, according to the authors there are still limitations and more research is warranted.

Reference:

1. Tomlins SA, Aubin SM, Siddiqui J, et al. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med. 2011 Aug 3;3:94ra72.