The University Record, April 15, 2002

U-M scientists find new genetic marker for prostate cancer

By Sally Pobojewski
Medical School Communications

Scientists at the Medical School have identified a gene that produces a specific protein in cancerous prostate cells, which could improve the accuracy and sensitivity of screening tests for prostate cancer—the second leading cause of cancer-related deaths in men.

The protein is an enzyme involved in fat metabolism called a-methylacyl-CoA racemase, or AMACR for short. AMACR has never before been associated with any type of cancer, according to Mark A. Rubin, associate professor of pathology and urology, and Arul M. Chinnaiyan, assistant professor of pathology and urology. Results from the study by Rubin and Chinnaiyan were published in the April 3 issue of the Journal of the American Medical Association.

“We detected high levels of AMACR protein in over 95 percent of more than 300 prostate tissue samples that contained localized cancer,” Chinnaiyan says.

“AMACR is one of approximately 20 genes which we found to be over-expressed consistently in prostate cancer,” Chinnaiyan adds. “This doesn’t mean that these genes cause prostate cancer, but they can be a marker or indicator of prostate cancer for diagnostic or prognostic purposes.”

AMACR’s accuracy and specificity is a major improvement over the Prostate Specific Antigen (PSA) test—the only diagnostic screening test currently available to physicians. “The beauty of AMACR is that it is cancer-specific and concentrated in malignant cells,” Rubin says. “PSA can’t differentiate between cell changes caused by cancer and those caused by benign changes in the prostate. As a result, PSA tests have a high rate of false positives, which can mean repeat needle biopsies and unnecessary surgery.”

U-M researchers say AMACR could act as a diagnostic marker for other types of cancer, too. When Rubin and Chinnaiyan surveyed cells from different types of cancer looking for AMACR over-expression, they found it in colorectal, prostate, ovarian, breast, bladder, lung, renal cell, lymphoma and melanoma with the highest amounts present in colorectal and prostate cancer.

Research on the genetic and molecular profile of prostate cancer using DNA microarray analysis is part of a major initiative under way in the U-M’s Comprehensive Cancer Center. Its goal is to link molecular genetics with clinical outcome for all types of cancer.

“Previous prostate cancer studies focused on one gene at a time,” Chinnaiyan says. “With DNA microarray technology, we can look at thousands of genes in prostate cells simultaneously. This is important, because it is most likely that many genes are involved in the development and progression of prostate cancer, each controlling a different step in the process.”

Since genetic and molecular profiling compares genes and proteins from normal cells to those from malignant cells in various stages, the U-M is developing other comprehensive tissue banks, so the technology can be applied to more types of cancer—including lung, ovarian, breast and colorectal cancer.

In future research, Rubin and Chinnaiyan plan to look for AMACR in a much larger number of prostate tissue samples from U-M and other institutions with SPORE tumor banks. Eventually, they hope to develop a blood test for AMACR, eliminating the need for needle biopsies of the prostate.

This research was supported by the National Cancer Institute and the U-M Bioinformatics Program. The U-M has applied for a patent on prostate cancer gene expression profiles for future diagnostic and therapeutic use.