Expression of claudin-7 and loss of claudin-18 correlate with poor prognosis in gastric cancer

Int J Surg. 2014;12(2):156-62. doi: 10.1016/j.ijsu.2013.11.022. Epub 2013 Dec 11.

Abstract

Background: The purpose of this study was to evaluate the expression of claudin-3, claudin-7, and claudin-18 in gastric cancer and to determine the significance of these proteins for patient outcome.

Materials and methods: A total of 134 samples were obtained from surgically resected specimens from patients who were diagnosed with gastric carcinoma at a single institution. Paraffin tissue sections from tissue microarray blocks were examined with immunohistochemistry for the expression of claudin-3, claudin-7, and claudin-18.

Results: In normal gastric tissues, positive immunoreactivity was detected for claudin-18 but not for claudin-3 or claudin-7. Claudin-3 and claudin-7 were expressed in 25.4% and 29.9% of the gastric cancer tissues, respectively. However, 51.5% of gastric cancer tissues exhibited reduced expression of claudin-18. Claudin-7 expression was significantly lower in cases with diffuse histologic type and positive lymphatic invasion. There was a significant inverse correlation between claudin-18 expression and perineural invasion. In the survival analysis, the overall survival time was shorter in patients with claudin-7 expression than in those without claudin-7 expression. However, the overall survival was longer in patients with claudin-18 expression than in those without claudin-18 expression.

Conclusions: Our data suggest that the up-regulation of claudin-3 and claudin-7 and the down-regulation of claudin-18 may play a role in the carcinogenesis of gastric cancer. Furthermore, the expression of claudin-7 and the loss of claudin-18 may be independent indicators of a poor prognosis in patients with gastric cancer.

Keywords: Claudin-18; Claudin-3; Claudin-7; Gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Claudins / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / metabolism*
  • Tissue Array Analysis

Substances

  • CLDN18 protein, human
  • CLDN7 protein, human
  • Claudins