Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expression patterns in gastric cancer

• Published in: Journal of cellular physiology 2007-01, Vol.210 (1), p.183-191
• Main Authors: Mattioli, Eliseo, Vogiatzi, Paraskevi, Sun, Ang, Abbadessa, Giovanni, Angeloni, Giulia, D'Ugo, Domenico, Trani, Daniela, Gaughan, John P, Vecchio, Fabio Maria, Cevenini, Gabriele, Persiani, Roberto, Giordano, Antonio, Claudio, Pier Paolo
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Blotting, Western; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p16 - analysis; Cyclin-Dependent Kinase Inhibitor p21 - analysis; Cyclin-Dependent Kinase Inhibitor p27 - analysis; DNA-Binding Proteins - analysis; Enhancer of Zeste Homolog 2 Protein; Female; Follow-Up Studies; Humans; Immunohistochemistry; Intestinal Neoplasms - chemistry; Intestinal Neoplasms - immunology; Intestinal Neoplasms - mortality; Intestinal Neoplasms - pathology; Ki-67 Antigen - analysis; Male; Middle Aged; Neoplasm Invasiveness; Polycomb Repressive Complex 2; Prognosis; Proportional Hazards Models; Retinoblastoma-Like Protein p130 - analysis; Stomach Neoplasms - chemistry; Stomach Neoplasms - immunology; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Transcription Factors - analysis; Tumor Suppressor Protein p53 - analysis; Vascular Endothelial Growth Factor A - analysis
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20833

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, p16(INK4A), p27(KIP1), p21(WAF1), 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 p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) 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.