Gene Predicts Prostate Cancer's Virulence
Could fine-tune diagnosis and prevent unnecessary treatments
WEDNESDAY, Oct. 9, 2002 (HealthDayNews) -- A gene that silences tumor-blocking proteins is a red flag for aggressive prostate cancer, new research says, and men having low levels of it could be spared unnecessary treatments.
The gene, EZH2, is much more active in aggressive prostate tumor cells than in either localized cancer or in healthy prostate tissue.
"This helps us distinguish between aggressive prostate cancer and slow-growing prostate cancer, and allows us to identify patients appropriate for watchful waiting and those who need radical [prostate removal surgery] or radiation," says Dr. Arul M. Chinnaiyan, a University of Michigan pathologist and leader of the research effort. The study appears as a research letter in tomorrow's issue of Nature.
Prostate cancer affects roughly 190,000 American men a year, killing 30,000. Metastatic prostate tumors are almost always lethal.
EZH2 belongs to a family of genes called transcription repressors, which prevent cells from copying and carrying out the instructions of other genes. It also belongs to a cluster of genes that help cells remember their specific function as they divide.
When Chinnaiyan's group boosted EZH2 protein levels in prostate cells in a dish, they saw that the activity of 163 other genes flagged -- yet no other genes revved up. Some of these genes that were shut down can help cells fight cancerous mutations.
In another experiment, when they disabled EZH2 with small bits of genetic material called RNA, cell division halted. "Not only is EZH2 likely involved in proliferation and progression, but it could serve as a therapeutic target, too," Chinnaiyan says. However, he adds, the researchers have yet to test that approach in lab animals or patients.
EZH2 is also present in certain forms of blood cancers such as lymphoma, though its utility as a marker for these diseases isn't clear.
Bruce Zetter, a cancer biologist at Children's Hospital in Boston who studies why tumors become metastatic, says EZH2 seems to behave like the first in a line of dominoes: Tipping it sends the whole array into a tumble.
Knowing which genes encourage the spread of cancer is valuable for all tumor types, but especially for prostate cancer, Zetter says, since the disease isn't deadly for most men.
"What we need in prostate cancer is a better prognostic marker. We don't need to improve the diagnosis so much," says Zetter, co-author of a commentary on the study. "That's what these latest developments are paving the way to do."
Doctors currently have little success at eradicating large tumors that have migrated from a main site, Zetter says. But in the future, thanks to early detection of smaller metastases, they will be able to use therapies like tumor vaccines and low doses of anti-cancer drugs to suppress these wanderers before they become deadly.
In earlier work, Chinnaiyan and his colleagues discovered a gene called AMACR, which could help solidify a diagnosis of prostate cancer in the event of a fuzzy biopsy. Such ambiguity occurs in about 15 percent to 20 percent of samples.
AMACR might also improve screening for prostate cancer, which is now done by a test for prostate-specific antigen, or PSA. This test picks up elevations in a blood protein shed by prostate tumors. Unfortunately, it's produced by benignly enlarged glands, too, leading to much unnecessary treatment.
AMACR, on the other hand, appears only to be elevated in the presence of cancer, so a positive result would signal a tumor.
Chinnaiyan is now working on combining AMACR and EZH2 into a single genetic test that would both identify the presence of prostate cancer and determine its virulence. The cost of such a test would not be exorbitant, he adds.
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