The prognostic impact of EGFR, ErbB2 and MET gene amplification in human gastric carcinomas as measured by quantitative Real-Time PCR

J Cancer Res Clin Oncol. 2015 Nov;141(11):1945-52. doi: 10.1007/s00432-015-1965-7. Epub 2015 Mar 29.

Abstract

Purpose: Identification of critical genes which play pivotal roles in controlling tumor growth and survival will establish the basis for developing therapeutic targets. In this study, we focused on frequencies of EGFR, ErbB2 and MET gene amplification in gastric cancer patients to develop personalized medicine to improve the treatment.

Method: EGFR, ErbB2 and MET gene amplification, and mRNA expression were analyzed by the quantitative Real-Time PCR in paraffin-embedded samples from 115 patients with gastric cancer.

Results: EGFR, ErbB2 and MET genes were amplified in 11.3 % (13/115), 6.1 % (7/115) and 19.1 % (22/115) of cancerous specimens, respectively. The correlation coefficient test clearly indicated that gene amplification in these three genes was positively correlated with mRNA transcription (EGFR: R = 0.631, p = 0.009; ErbB2: R = 0.652, p = 0.023; MET: R = 0.715, p < 0.001). EGFR and MET gene amplification was significantly associated with Ki-67 MI (p = 0.022 and p = 0.015). MET amplification was also significantly associated with age of ≥60 years (p = 0.021) and tumor size of ≥5 cm (p = 0.032). MET amplification, but not EGFR and ErbB2, was a significant prognostic factor in poor survival among patients with gastric cancer.

Conclusions: EGFR, ErbB2 and MET genes are frequently amplified in gastric carcinoma. EGFR, ErbB2 and MET gene amplification is positively correlated with mRNA transcription. MET gene amplification correlates with a poor prognosis and poor survival in gastric carcinomas.

Keywords: EGFR; ErbB2; Gastric cancer; Gene amplification; MET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Copy Number Variations / genetics
  • ErbB Receptors / genetics*
  • Female
  • Gene Amplification*
  • Gene Dosage
  • Humans
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-met / genetics*
  • RNA, Messenger / biosynthesis
  • Real-Time Polymerase Chain Reaction
  • Receptor, ErbB-2 / genetics*
  • Stomach Neoplasms / genetics*

Substances

  • RNA, Messenger
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2