Researchers at Jefferson Medical College have found that the less a particular "protective" gene is present in endometrial cancer cells, the more aggressive the disease will be, and the greater the likelihood the woman will die from the disease. The finding may eventually lead to a test that can predict disease severity and help guide treatment.
Antonio Giordano, M.D., Ph.D., associate professor of pathology, anatomy and cell biology at Thomas Jefferson University, in Philadelphia and his colleagues there and at the University of Florence and at the Second University of Naples examined the cancer cells of 100 patients who underwent surgery for endometrial cancer. The patients had no prior radiation or chemotherapy.
They found that five years after surgery, lower levels of the tumor suppressor gene Rb2/p130 correlated with a higher risk than normal of returning disease. The women were also more likely to die of the cancer. They report their findings in the March issue of the Journal of Clinical Oncology.
"We measured Rb2/p130 status in relation to the length of disease-free survival and disease-specific survival in 100 endometrial cancer patients who had surgery to remove the tumor," explains Dr. Giordano, who also is president of the Sbarro Institute for Cancer Research and Molecular Medicine, which is affiliated with Jefferson Medical College. "We found a decreased level of pRb2 in endometrial cancer significantly associated with decreased probability of remaining disease-free.
"We found that the risk of dying from endometrial cancer was four and a half times more likely in women with these lower levels of the gene," he points out. "In patients with endometrial cancer, and who haven’t had chemotherapy or radiation before surgery, the presence of Rb2 is associated with a higher risk of dying independent of the stage of the disease.
"This is the first report that Rb2/p130 levels have been associated with survival with endometrial cancer." A diagnostic test could be developed within a few years, he suggests.
"These findings lend further support to the idea that pRb2 is a strong factor that protects normal cells from turning cancerous," he notes. The gene has also been linked to other cancers, such as lung, bladder, osteosarcoma, breast and cervical. Dr. Giordano and his colleagues suspected an Rb2-endometrial cancer link because they had seen similar mechanisms in lung cancer. "If this mechanism is common in lung and endometrial cancers," he notes, "it may be involved in some way in other cancers. These additional results put Rb2 in a restricted group of identified genes vital to the normal function of cells in our body."
Dr. Giordano thinks the findings may someday help doctors identify which women are at greater risk of recurring disease. As a result, they may be better able to select which endometrial cancer patients should have less aggressive surgery, and which individuals may be at higher risk for recurrence, perhaps requiring more treatment. "Lower pRb2 levels may indicate the need for more aggressive treatment for potentially recurrent disease," he explains. "A high level may indicate less aggressive therapy is needed. Rb2 may be useful as a prognostic indicator to help set the course of therapy. Our results may influence the selection of candidates for less aggressive surgical treatment. They may also be helpful in identifying high-risk patients to whom every surgery effort should be attempted.
"We need to follow large groups of patients and randomize them, including patients who have had chemotherapy and/or radiation either pre- or post-operatively. [The findings] may allow physicians to intervene in a more appropriate manner."
He explains that pRb2 is involved in the regulation and control of the cell cycle and cell division. "We know that when it [pRb2] doesn’t function properly, cell division goes awry." Further prospective studies are needed before a potential test is ready for clinical use, he adds.
Endometrial cancer is the most common cancer of the female reproductive tract. As with many cancers, endometrial cancer is much more treatable when caught in its earliest stage. The American Cancer Society (ACS) estimates that roughly 36,000 new cases of endometrial cancer will be diagnosed in the United States during 1998. Some 6,300 U.S. women will die from the disease this year.
Journal
Journal of Clinical Oncology