Low Level of p27 Predicts
Aggressive Disease

December 15, 1998. If prostate cancer patients could be tested to find out how aggressive their cancer might be, they and their doctors could make much better choices about the type of treatment likely to be most effective. A protein pinpointed recently may help do just that — predict whether a given prostate tumor might grow and spread quickly, or take a slower course.
     The protein in question, p27, normally acts to suppress tumor growth. Identified by Dr. Andrew Koff, of the Memorial Sloan-Kettering Institute's Molecular Biology Program, when he was an investigator at the Fred Hutchinson Cancer Research Center, it was cloned by Dr. Joan Massagué, MSKI's Program Chairman for Cell Biology.
     By analyzing different types of prostate tissue, the researchers found that prostate cancers with low levels of p27 are highly aggressive. Patients with these aggressive prostate cancers are likely to have a higher rate of cancer recurrence. These patients face worse chances for long-term survival. In contrast, patients whose prostate tumors contain plenty of p27 are likely to do better, because the tumor is slow-growing.
     "At the molecular level, we saw alterations resulting in two different types of prostate cancer," said Dr. Carlos Cordon-Cardo, Director of MSK's Division of Molecular Pathology and a co-author of the report. "Our study reinforces previous research suggesting that prostate cancer can develop along two different pathways — one involving the loss of p27 and the other using processes that circumvent the growth-suppressive effects of p27."
     The finding of variable levels of p27 is expected to make it easier to know how much treatment to give an individual patient. "Knowledge of the prognosis of an individual patient can help determine who needs additional therapy to improve the chance of cure," said Dr. Howard I. Scher, Chief of MSK's Genitourinary Oncology Service and another co-author of the study.
     The scientists found that prostate tissue has varying levels of the messenger RNA (mRNA) for p27, the intermediary between the gene for p27 and the protein itself. Normal prostate tissue has an abundance of both p27 and its corresponding mRNA. Men with benign prostatic hyperplasia (BPH, or enlargement of the prostate) have undetectable levels of both p27 and its mRNA, while those with prostate cancer have abundant mRNA but variable levels of p27.
     The finding that p27 and its mRNA are missing in BPH shows that BPH is genetically different from prostate cancer. "This result supports the hypothesis that BPH and prostate cancer develop along different pathways," Dr. Scher said.

The finding of variable levels of p27 in prostate cancer confirms earlier work done by MSK and Norris Cancer Center researchers while working together at University of Southern California. The study results were published in the Journal of the National Cancer Institute.