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

D. A. Heideman, P. J. Snijders, E. Bloemena, C. J. Meijer, G. J. Offerhaus, S. G. Meuwissen, W. R. Gerritsen, M. E. Craanen

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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 or 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
Pages (from-to)428-435
Number of pages8
JournalJournal of pathology
Volume194
Issue number4
DOIs
Publication statusPublished - Aug 2001

Keywords

  • Adenocarcinoma
  • Cell Transformation, Neoplastic
  • Gastric Mucosa
  • Gene Expression
  • Gene Rearrangement
  • Humans
  • Journal Article
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-met
  • RNA, Messenger
  • RNA, Neoplasm
  • Research Support, Non-U.S. Gov't
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Stomach Neoplasms
  • Tumor Cells, Cultured

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