Characterizing Metastatic HER2-Positive Gastric Cancer at the CDH1 Haplotype

Int J Mol Sci. 2017 Dec 23;19(1):47. doi: 10.3390/ijms19010047.

Abstract

The CDH1 gene, coding for the E-cadherin protein, is linked to gastric cancer (GC) susceptibility and tumor invasion. The human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in a portion of GC. HER2 is an established therapeutic target in metastatic GC (mGC). Trastuzumab, in combination with various chemotherapeutic agents, is a standard treatment for these tumors leading to outcome improvement. Unfortunately, the survival benefit is limited to a fraction of patients. The aim of this study was to improve knowledge of the HER2 and the E-cadherin alterations in the context of GC to characterize subtypes of patients that could better benefit from targeted therapy. An association between the P7-CDH1 haplotype, including two polymorphisms (rs16260A-rs1801552T) and a subset of HER2-positive mGC with better prognosis was observed. Results indicated the potential evaluation of CDH1 haplotypes in mGC to stratify patients that will benefit from trastuzumab-based treatments. Moreover, data may have implications to understanding the HER2 and the E-cadherin interactions in vivo and in response to treatments.

Keywords: CDH1; E-cadherin; HER2; metastatic gastric cancer; rs16260; rs1801552.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD
  • Base Sequence
  • Cadherins / genetics*
  • Female
  • Gene Frequency / genetics
  • Germ-Line Mutation / genetics
  • Haplotypes / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Survival Analysis

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • ERBB2 protein, human
  • Receptor, ErbB-2