Archives|A Protein Is Said to Predict Prostate Cancer's Virulence
By JANE E. BRODY SEPT. 2, 1998
Researchers at the Memorial Sloan-Kettering Cancer Center in New York have found that a protein seems to predict which prostate cancers are likely to be deadly and warrant aggressive treatment and which can be controlled with less treatment or perhaps none at all.
The new findings, published this week in The Journal of the National Cancer Institute, also support the current understanding that benign enlargement of the prostate, which occurs in many men as they age, is an entirely separate development from prostate cancer and does not lead to it.
The studies involve a protein called p27, which other research suggests plays an important role in controlling the growth of many cancers that arise in lining tissues throughout the body. Studies in Boston, Seattle, Toronto and England have linked abnormally low levels of the p27 protein to aggressive cancers of the breast, the colon, the lung and the esophagus.
''This protein represents a common mechanism that helps to control and regulate cell growth,'' explained Dr. Howard Scher, who directs genitourinary oncology at Memorial Sloan-Kettering. ''It may help us predict who will be cured and who won't, and help determine who may need additional treatment to improve the chance of cure.''
Dr. Carlos Cordon-Cardo, director of molecular pathology at Sloan-Kettering, said p27 acted like a brake that kept cell growth in check. When levels of this protein are low or absent, cells are likely to proliferate rapidly. Rapid cell growth can increase the chances of genetic mutations that may allow a cancer to develop and grow uncontrolled.
Dr. Cordon-Cardo explained that men with prostate cancer have a normal gene that regulates the production of the p27 protein. But in those with an aggressive prostate cancer that is most likely to spread and be fatal, the tumor seems to have ''a professional blender'' that chews up the protein. In men with less aggressive tumors that may be curable without extensive treatment, p27 levels are much higher, he said.
''Two tumors may look alike under the microscope,'' Dr. Cordon-Cardo said, and ''yet one patient may go on for years without the cancer spreading, and the other may die of his cancer in two years. If we can prognosticate at the time of diagnosis, we can determine who should be treated more aggressively.''
In treatment of prostate cancer, the choices include radical surgery, radiation therapy, radioactive implants, hormonal control and chemotherapy, all of which involve varying degrees of both short-term and long-lasting side effects.
The emerging understanding of p27's role in cancer grows out of previous work by Dr. Joan Massague and Dr. Andrew Koff, molecular biologists at Sloan-Kettering who first isolated and cloned the protein. Dr. Koff showed that mice without the p27 gene developed overgrowth of the prostate gland, similar to the growth that occurs in men with benign prostatic hyperplasia.
In men with this benign condition, the p27 gene is inactive, and little or no p27 protein is produced. In men with prostate cancer, on the other hand, the gene is active, but in some cases the tumor has the ability to chew up the protein that the gene produces.
The degradation of p27 protein by cancers of the colon was first described last year by Dr. Massimo Loda of the Dana-Farber Cancer Institute in Boston and Dr. Miguele Pagano of New York University. Dr. Loda said that in colon cancer patients who initially had high levels of the protein but whose tumors spread years later, the protein was lost in the process of metastasis.
''We also found that p27 protein was involved in lung cancers and breast cancers,'' Dr. Loda said.
Dr. Scher, of Sloan-Kettering, suggested that in the future it might be possible to identify a switch that would enable the p27 protein to remain active and slow the growth of tumor cells.