Transforming growth factor beta type II receptor expression in gastric cancer: evidence for two independent subgroups.

Transforming growth factor beta type II receptor (TGFbeta-IIR) has been found to be altered in primary gastrointestinal carcinomas. So far relatively few facts are known about the expression of TGFbeta-IIR in primary gastric cancer. Therefore, in the present study, TGFbeta-IIR expression was analyzed in 130 primary gastric carcinomas and correlated with clinicopathological findings, the presence of a mutator phenotype, the mutational status of the TGFbeta-IIR polyadenine tract and survival. TGFbeta-IIR expression was analyzed immunohistochemically. Microsatellite instability was evaluated using a PCR-based assay and the polyadenine run inside the TGFbeta-IIR gene was sequenced. A complete loss of TGFbeta-IIR expression could be found in 55 (42.3%) of these carcinomas. Loss of TGFbeta-IIR expression was significantly correlated with diffuse-type carcinomas according to the Lauren classification as well as with signet ring cell carcinomas and a lower grade of differentiation. No correlation was found with the overall prognosis, the presence of a mutator phenotype, or a mutated TGFbeta-IIR. Thus, our data suggest the existence of a further definite subgroup of diffuse-type gastric carcinomas with altered TGFbeta-IIR expression, independent from a mutator phenotype with TGFbeta-IIR gene mutations. However, according to our results, in gastric cancer neither loss of TGFbeta-IIR expression nor mutations of the TGFbeta-IIR are of prognostic value.