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

The c-met proto-oncogene, encoding the hepatocyte growth factor receptor, c an be activated by various mechanisms. These include, among others, gene am plification with concomitant/overexpression and the tpr-met oncogenic rearr angement. In the case of gastric cancer, contradictory results on the prese nce of the tpr-met oncogenic rearrangement have been published. The current study aimed therefore to assess the prevalence of tpr-met expression in Ca ucasian gastric adenocarcinomas, to evaluate the importance of this oncogen e in their carcinogenesis. In addition. the level of c-met expression was d etermined. to evaluate the role of this alternative mode of activation of t he proto-oncogene. A series of Caucasian gastric adenocarcinomas (n = 43) a nd normal gastric mucosal samples (n = 14) was analysed for tpr-met and e-m et expression. Expression of tpr-met mRNA in the samples was performed by t wo reverse transcriptase polymerase chain reaction (RT-PCR) assays, with ex cellent correlation. The specificity of both methods was confirmed by direc t 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 us ing 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 ade nocarcinomas showed overexpression of c-met, according to elevated c-met mR NA levels, compared with the expression level of normal gastric mucosa. A s ignificant correlation was found between the level of c-met mRNA and protei n expression. In conclusion, these results strongly suggest that tpr-met ac tivation does not play a role in Caucasian gastric carcinogenesis, while ov erexpression of the e-met gene occurs in the majority of Caucasian gastric adenocarcinomas. Copyright (C) 2001 John Wiley & Sons, Ltd.