Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis

APMIS. 2003 Dec;111(12):1105-13. doi: 10.1111/j.1600-0463.2003.apm1111205.x.

Abstract

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / metabolism
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Smad4 Protein
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • Trans-Activators / metabolism

Substances

  • Adenomatous Polyposis Coli Protein
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt