Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma

Danille A.M. Heideman, Peter J.F. Snijders, Elisabeth Bloemena, Chris J.L.M. Meijer, G. Johan A Offerhaus, Stefan G.M. Meuwissen, Winald R. Gerritsen, Mikael E. Craanen

Research output: Contribution to journalArticlepeer-review

Abstract

The c-met proto-oncogene, encoding the hepatocyte growth factor receptor, can be activated by various mechanisms. These include, among others, gene amplification with concomitant overexpression and the tpr-met oncogenic rearrangement. In the case of gastric cancer, contradictory results on the presence of the tpr-met oncogenic rearrangement have been published. The current study aimed therefore to assess the prevalence of tpr-met expression in Caucasian gastric adenocarcinomas, to evaluate the importance of this oncogene in their carcinogenesis. In addition, the level of c-met expression was determined, to evaluate the role of this alternative mode of activation of the proto-oncogene. A series of Caucasian gastric adenocarcinomas (n = 43) and normal gastric mucosal samples (n = 14) was analysed for tpr-met and c-met expression. Expression of tpr-met mRNA in the samples was performed by two reverse transcriptase polymerase chain reaction (RT-PCR) assays, with excellent correlation. The specificity of both methods was confirmed by direct sequencing of the PCR products of the MNNG-HOS cell line, which is known to contain the rearrangement. The level of c-met expression was assessed using semi-quantitative RT-PCR assays and immunohistochemistry (IHC). None of the normal gastric mucosal of gastric adenocarcinoma samples expressed tpr-met mRNA, as determined by both RT-PCR assays. Seventy per cent of the adenocarcinomas showed overexpression of c-met, according to elevated c-met mRNA levels, compared with the expression level of normal gastric mucosa. A significant correlation was found between the level of c-met mRNA and protein expression. In conclusion, these results strongly suggest that tpr-met activation does not play a role in Caucasian gastric carcinogenesis, while overexpression of the c-met gene occurs in the majority of Caucasian gastric adenocarcinomas.

Original languageEnglish (US)
Pages (from-to)428-435
Number of pages8
JournalJournal of Pathology
Volume194
Issue number4
DOIs
StatePublished - Jan 1 2001

Keywords

  • C-met proto-oncogene
  • Gastric cancer
  • Hepatocyte growth factor receptor
  • Immunohistochemistry
  • RT-PCR
  • Tpr-met oncogenic rearrangement

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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