Expression of gastrin and its receptor in human gastric cancer tissues

J Cancer Res Clin Oncol. 2006 Feb;132(2):85-91. doi: 10.1007/s00432-005-0043-y. Epub 2005 Oct 14.

Abstract

Purpose: Gastrin is a growth factor of cancerous and normal cells of the gastrointestinal tract, and its effect is known to be mediated by gastrin/cholecystokinin B (CCKB) receptor. This study was performed to investigate the prognostic significance and the expression profiles of gastrin and gastrin receptor in human gastric carcinoma tissues.

Methods: We analyzed the expressions of gastrin and gastrin receptor by immunohistochemical staining using anti-gastrin Ab (Sigma, St. Louis, MO, USA) and anti-gastrin receptor Ab (Aphton Corp., Woodland, CA, USA) in 279 gastric adenocarcinoma patients. Patients' clinicopathologic features and prognoses were analyzed.

Results: The gastrin expression rate in these patients was 47.7% (133/279) and the gastrin receptor expression rate was 56.5% (158/279). Gastrin expression was significantly higher in men than in women (54.3% vs. 34.1%), and higher in differentiated gastric adenocarcinoma than in the undifferentiated type (55.1% vs. 43.0%). The gastrin receptor expression rate was also significantly higher in men than in women (61.2% vs. 47.3%), and was higher in the differentiated type than in the undifferentiated type (72.9% vs. 46.5%), and significantly higher in the intestinal type than in the diffuse type (75.2% vs. 42.9%). Gastrin and gastrin/CCKB receptor expressions were not found to be significant prognostic factors in themselves. When focused on correlation between the co-expression of gastrin and gastrin/CCKB receptor and the survival, the prognosis of patients positive for both gastrin and gastrin receptor was significantly poorer than for those negative for gastrin and gastrin receptor in diffuse-type gastric cancer patients. However, multivariate analysis showed that only TNM stage was an independent prognostic factor of survival in diffuse-type gastric cancer patients.

Conclusions: This study shows that the expression rates of gastrin and gastrin receptor are high (about a half) in gastric carcinoma tissues, and that there is an association between gastrin and gastrin receptor expression. We also found that patients with diffuse-type gastric carcinoma tissues expressing both gastrin and gastrin receptor have a poorer prognosis than those negative for both, which suggests that gastrin acts as an autocrine growth factor in a subgroup of gastric carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Female
  • Gastrins / analysis*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Receptor, Cholecystokinin B / analysis*
  • Sex Factors
  • Stomach Neoplasms / chemistry*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Gastrins
  • Receptor, Cholecystokinin B