The angiotensin II/angiotensin II receptor system correlates with nodal spread in intestinal type gastric cancer

Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1206-12. doi: 10.1158/1055-9965.EPI-05-0934.

Abstract

We aimed to substantiate the putative significance of angiotensin II receptor type 1 (AT1R) and type 2 (AT2R) for gastric cancer biology by investigating the correlation of their expression with various clinicopathologic variables and patient survival. Local expression of AT1R, AT2R, and angiotensin-converting enzyme (ACE) was investigated by immunohistochemistry in tumor and corresponding nontumor specimens obtained from 100 patients with gastric cancer, and compared with the ACE insertion/deletion gene polymorphism. AT1R and AT2R were found in the tumor epithelial cells of 26 (26%) and 95 (95%) patients, respectively. AT1R was significantly more prevalent (P < 0.001) in intestinal type gastric cancer than in diffuse type gastric cancer. In intestinal type gastric cancer, its expression correlated with the N category (P = 0.009) and the International Union Against Cancer tumor stage (P = 0.024). AT1R+ intestinal type gastric cancers had a larger number of lymph node metastases (P = 0.026), a higher International Union Against Cancer tumor stage (P = 0.032), and a shorter survival time (P = 0.009) than AT1R- tumors. Multivariate analysis with lymph nodes as a dependent variable showed that AT1R status and ACE-I/D gene polymorphism are independent risk factors. Irrespective of the genotype, AT1R+ gastric cancers had a relative risk of lymph node metastases of 4.40 (95% confidence interval, 1.30-14.86). When the ACE genotype was included, the relative risk of having lymph node metastases increased considerably in AT1R+ tumors being heterozygous or homozygous for the ACE D allele (odds ratio, 19.00; 95% confidence interval, 1.45-248.24). Our study shows that AT1R and AT2R are expressed locally in gastric cancer and that the combination of AT1R expression and ACE I/D gene polymorphism correlates with nodal spread in intestinal type gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Aged
  • Angiotensin II / metabolism*
  • Female
  • Gene Expression
  • Genetic Predisposition to Disease*
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Polymerase Chain Reaction
  • Receptors, Angiotensin / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • Receptors, Angiotensin
  • Angiotensin II
  • Peptidyl-Dipeptidase A