WEDNESDAY, Aug. 22, 2001 (HealthDayNews) -- In a kind of molecular handwriting analysis, scientists soon may be able to screen prostate tissue for the genetic signatures of cancer.
Michigan scientists say they've discovered two genes, and potentially many others, that could help identify men with prostate tumors. What's more, the researchers say the two markers appear to reflect both the presence and the virulence of the cancer -- perhaps providing physicians with a tool to better guide treatment.
"Our goal is to see if we can identify a cohort of these proteins that can tell a clinician whether a patient's prostate cancer is indolent or aggressive," says Dr. Arul Chinnaiyan, a University of Michigan pathologist and lead author of a research letter in the Aug. 23 issue of Nature. Ultimately, Chinnaiyan says there probably will be 10 to 100 different genes to test in each prostate tissue sample. "We're working on many more that we've identified," he says.
Prostate cancer is the most common cancer in men, killing 40,000 of the 180,000 Americans diagnosed with the disease each year.
Chinnaiyan and his colleagues looked for genetic anomalies in prostate tissue samples from 50 men, including 18 with various degrees of prostate cancer. The rest had normal or enlarged but otherwise healthy prostate glands.
Using computers to screen the tissue samples, the researchers identified some 200 genes or gene fragments whose presence appeared to vary depending on whether the cells were healthy or malignant. Of those, they found two genes, hepsin and pim-1, that weren't previously linked to prostate cancer.
"With normal tissue there was negative or very weak staining but cancer had either weak to very strong staining," Chinnaiyan says. Staining is a tool that allows researchers to identify the presence of a gene in cell samples.
Kurt Borg, a prostate cancer researcher at the University of North Dakota, says pim-1 is expressed in immune cells called lymphocytes, which are abnormally long-lived when cancerous. Intriguingly, he says both lymphocytes and prostate tissue are sensitive to the hormone prolactin, a substance made in the brain's pituitary gland that, in mammals, signals mammary glands to produce milk.
"Maybe it's the same mechanism" controlling both lymphocytic leukemia and prostate cancer, he says.
The Michigan researchers also looked at more than 700 cell samples collected from prostate cancer patients to see if the two markers reflected the clinical progress of the disease.
Hepsin, a so-called transmembrane serine protease enzyme, isn't very well understood. But the Michigan scientists say it may play a role in early tumor formation, since it shows up more strongly in fledgling tumors than in established or spreading ones. "It's needed for early on establishment of the tumor," Chinnaiyan says.
Pim-1, on the other hand, is a well-known cancer gene associated with certain leukemias, or blood and marrow cancers, although researchers hadn't previously tied it to solid tumors.
The protein, which belongs to a family of enzymes called serine/threonine kinases, appeared more prominently in tissue samples from men with advanced or metastatic disease. It also cropped up in tandem with another known cancer gene, called MYC, that is over-expressed in prostate tumors. "We suspect that in the context of prostate cancer there might be some synergy" with the two genes, Chinnaiyan says.
Chinnaiyan says it's possible that chemical castration therapy might have influenced levels of the two genes in some samples so the group is now collecting samples of metastatic prostate cancer from men in Europe who have not undergone such aggressive treatment.
Doctors now screen men for prostate cancer with a blood test for a protein called prostate-specific antigen, or PSA. But the two new genes aren't found in blood, so to look for them doctors would have to examine tissue to detect their presence, Chinnaiyan says.
What To Do
If you're 50 or older, you should have a PSA test every year. Men with a history of prostate cancer in their families should start getting the blood exam even earlier.
To learn more about prostate cancer, try the University of Pennsylvania or CAPCURE.
You can also get more information from the National Cancer Institute.
