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

J Cell Physiol. 2007 Jan;210(1):183-91. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Retinoblastoma-Like Protein p130
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cyclin-Dependent Kinase Inhibitor p27
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2