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Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16INK4A, p27KIP1, p21WAF1, Ki‐67 expression patterns in gastric cancer

Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16INK4A, p27KIP1, p21WAF1, Ki‐67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal‐type, and 20 of diffuse‐type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO‐III, and YCC‐2, ‐3, ‐16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki‐67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal‐type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27KIP1 expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21WAF1 and low‐grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor‐suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low‐grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials. J. Cell. Physiol. 210: 183–191, 2007. © 2006 Wiley‐Liss, Inc.