New York, N.Y., September 1, 1998 -- In a study of the protein p27, researchers at Memorial Sloan-Kettering Cancer Center have confirmed the existence of at least two different types of prostate cancer. One is a more aggressive form of the disease with a higher rate of recurrence and poorer long term survival. Researchers believe that this information can help in determining the patient's prognosis which may affect treatment selection.
Researchers also discovered that p27 plays a distinct role in Benign Prostate Hyperplasia (BPH) which was found to be genetically different from prostate cancer. This supports the thesis that it is not a precursor to the development of prostate cancer.
The study, published in the September Journal of the National Cancer Institute, involved the examination of the levels of p27 protein in one hundred and thirty tissue samples of patients with prostate cancer as well as samples from normal men and patients with BPH.
The p27 protein, first discovered by study co-authors Dr. Joan Massagué, chairman of the Cell Biology Program at Memorial Sloan-Kettering and Dr. Andrew Koff of the Molecular Biology Program, is one of the proteins generically called a cell cycle inhibitor. It is a potential tumor suppressor. Normal prostate tissue has abundant amounts of both p27 protein and its messenger RNA (p27KIP1 mRNA), the intermediary between the gene and the protein. However, both messenger and protein are undetectable in patients with BPH. In contrast, patients with prostate cancer have abundant p27KIP1mRNA but p27 protein levels were variable - high in some cases or very low to undetectable in others. Investigators found that prostate cancers with the lower levels of p27 were more aggressive.
"Our study reinforces previous research that suggests 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," said Dr. Carlos Cordon-Cardo, director of the Division of Molecular Pathology at Memorial Sloan Kettering and a co-author of the study. "At the molecular level, we saw alterations resulting in two different types of prostate cancer. Cancers with a lower level of p27 had a biologically more aggressive disease associated with a higher rate of recurrence and a greater risk of death."
The finding confirms collaborative research conducted by Memorial Sloan-Kettering Cancer Center and the Norris Cancer Center at the University of Southern California in Los Angeles. "Knowledge of the prognosis of an individual patient can help determine who needs additional therapy to improve their chance of cure," explained Dr. Howard Scher, chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering and a co-author.
BPH Found Not to be a Precursor to Prostate Cancer
In a related finding, researchers found that p27 was completely absent at both the gene messenger (mRNA) level and the protein level in prostate tissues of patients with BPH. "This supports the hypothesis that BPH is not a premalignant lesion in the development of prostate cancer," said Dr. Scher.
The research built on the previous work of the study's co-authors, Dr. Joan Massagué and Dr. Andrew Koff of the Molecular Biology Program. Dr. Massagué was the first to isolate and clone the p27 protein, a key cell cycle inhibitor essential to arresting cell growth. Dr. Koff was the first to produce genetically engineered mice without the p27 gene. Studies on the "null" mice indicated that p27 played a major role in the cells' response to signals to stop cell growth and promote growth arrest. They developed prostatic hyperplasia similar to that found in human males, producing genetic evidence that the loss of p27 expression in prostatic tissue of elderly men may be causally linked to BPH.
Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer.
Throughout its long distinguished history, the Center has played a leadership role in defining the standard of care for patients with cancer. In 1998, Memorial Sloan-Kettering was named the nation's best cancer care center for the sixth consecutive year by U.S. News & World Report.
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Journal
JNCI Journal of the National Cancer Institute