Expression of Rb2/p130 and VEGF could serve as potential liver cancer prognosticators

May 15, 2004

The expression of the tumor-suppressing gene Rb2/p130 and the protein Vascular Endothelial Growth Factor (VEGF) in hepatocellular carcinoma (liver cancer) could serve as important independent prognostic markers in determining the aggressiveness of the cancer, according to researchers at the Sbarro Institute for Cancer Research and Molecular Medicine in the Center for Biotechnology at Temple University (http://www.shro.org).

The results of their study, "pRb2/p130, VEGF, p27(KIP1) and PCNA expression in hepatocellular carcinoma: their clinical significance," will be published in the May 15 issue of Clinical Cancer Research (http://clincancerres.aacrjournals.org).

In the study, which was led by Pier Paolo Claudio, M.D., Ph.D., associate professor of biotechnology at the Sbarro Institute at Temple, the researchers examined 21 cases of hepatocellular carcinoma in order to analyze potential molecular biomarkers that may be useful as prognostic indicators for the cancer, which is one of the most prevalent malignancies worldwide and the third-largest cause of cancer deaths. The researchers discovered an inverse correlation between the expression of Rb2 and VEGF in the tumors.

"We examined a panel of 21 tumors and found some of them had a little Rb2 expression and some of them had no Rb2 expression," says Claudio, the study's lead author. "And all of this correlated with an opposite level of VEGF in each sample."

According to Claudio, the lower the Rb2 expression and the higher the VEGF expression, the more aggressive the liver cancer. He adds that the Temple researchers' findings were the same, regardless of whether the tumor was in an early or an advanced stage.

"Rb2 and VEGF expression are independent from the tumor's stage of development, suggesting these two proteins play a potential role as prognostic markers because they are going to indicate the aggressiveness of the cancer," says Claudio.

"Using these two biomarkers together could be a more universal way to screen hepatocellular carcinoma because no matter what the tumor stage, they are going to be good prognosticators," adds Giuseppe Russo, Ph.D., a research fellow at the Sbarro Institute.

Antonio Giordano, M.D., Ph.D., director of the Sbarro Institute and co-director of the Center for Biotechnology, says that the analysis of Rb2 and VEGF expression could be a powerful tool in the hands of physicians, helping them to determine how aggressive the cancer will be and thus to better tailor therapies for individuals.

"The liver is very important because it is our body's filter," says Claudio. "There is still no real cure for hepatocellular carcinoma. Patients often get operated on, but ultimately, the only real hope is a liver transplant and unfortunately, there are only so many liver donors.

"The physician could now better understand and predict how the tumor is going to behave based on the molecular analysis of these two independent prognostic markers," he adds.

The study was carried out at Temple's Sbarro Institute in collaboration with Catholic University of the Sacred Heart and the universities of Naples and Siena in Italy, and Drexel University's College of Medicine. It was funded by the National Institutes of Health, the Sbarro Health Research Organization, and the W.W. Smith Charitable Trust Foundation.
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Temple University

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