Diffuse gastric cancer: Key tumor suppressor is set off nuclear stage

The study, published in the Journal of Cellular Physiology, was led by the research team of Antonio Giordano, a pathologist, Director and Founder of the Sbarro Health Research Organization in Philadelphia, PA (www.shro.org) and Professor of Pathology and Oncology at the University of Siena, Italy.

Giordano's group set up to study the expression and localization of the pRb2/p130 protein, an important tumor suppressor that Giordano himself identified in 1993, in gastric tumors. Although epidemiologic studies show that gastric cancer incidence is decreasing worldwide, it still represents the fifth most common cancer worldwide and an important cause of many cancer-related deaths. Here the authors focused specifically on a particular variant, gastric cancer of the diffuse histotype, which shows undifferentiated morphology, the lack of precursor lesions, occurs most commonly in young patients and has a poor prognosis.

The researchers found that in these tumors pRb2/p130 is mostly confined to the cell cytoplasmic compartment whereas in the surrounding normal tissue it localizes to the nucleus where it generally plays its part as tumor suppressor acting as a break to cell proliferation.

Previous studies of Giordano have shown that pRb2/p130 delocalization to the cytoplasm in other tumor types correlates with tumor aggressiveness. For example in salivary gland tumors cytoplasmic expression of pRb2/p130 correlates with tumor grading, with the presence of metastasis and with a decreased probability of survival. "Our results show that pRb2/p130 delocalization might have an important role also in gastric tumorigenesis. Further studies will also assess whether pRb2/p130 analysis could be a useful clinical tool as diagnostic or prognostic factor for diffuse gastric cancer," says Letizia Cito, researcher at CROM, of the National Cancer Institute of Naples, and first author of the manuscript.

"In our lab we are also exploring new therapeutic strategies aimed at reactivating pRb2/p130 tumor suppressor function in cancer. This study definitively adds diffuse gastric adenocarcinomas to the list of tumors that could potentially be targeted by these agents, which are currently under development in the preclinical stage," Giordano concludes.