Article
Ann Arbor, MI--Researchers at the University of Michigan Medical School are developing a new test for prostate cancer, one that takes advantage of the sensitivity of the immune response. If the test achieves only a portion of its promise, it will have a significant impact on false-positive results generated by the current PSA screening test and on the unnecessary biopsies that subsequently follow.
The test involves a combination of technologies that identifies the autoantibody signature of the disease. Initial experimentation with serum samples drawn from the University of Michigan's tissue and serum library shows the test to have a specificity of 88.2% and a sensitivity of 81.6%, as reported recently in the New England Journal of Medicine (2005; 353:1224-35). PSA tests have a specificity of around 80% and a sensitivity of around 30% to 35%. This latter aspect of the test is responsible for a significant number of false positives and subsequent unnecessary biopsies.
The new test is at the experimental stage, which means its applications and limitations are anyone's guess.
The research was led by Arul M. Chinnaiyan, MD, PhD, professor of pathology at the University of Michigan. Additional authors included urologists from Beth Israel-Deaconess Medical Center and the Dana-Farber Cancer Institute, both in Boston.
Dr. Montie enumerated several possible applications for the test.
"It has a lot of potential. It could eliminate the need for biopsy in some men with abnormal PSA. It could be useful in men who have low PSAs. It may correlate with the extent of the disease, the aggressiveness of the cancer, or the size of the tumor. All of these issues need to be addressed," he said.
The reason for this broad potential lies with the ability of the test to acquire a snapshot of the immune system response to the presence of cancer. It provides a visual pattern of antibodies that is characteristic of prostate cancer and no other disease process.
The immune system may mount an antibody response when the cancer is no more than a smattering of cells.
Researchers worked through three distinct phases in developing the test: discovery, training, and validation.
In the discovery phase, they randomly selected 150 of 331 serum samples drawn from men known to have prostate cancer. The samples were washed across a 2,304-phage protein microarray. This is an array of bacteriophages, each of which holds a gene that produces a known peptide associated with prostate cancer. These peptides serve as bait to capture antibodies in the serum samples.