Gastrin and gastrin receptor activation: an early event in the adenoma-carcinoma sequence

Background and aims-Gastrin and the cholecystokinin type B/gastrin receptor (CCKBR) have been shown to be expressed in colorectal adenocarcinoma. Both exogenous and autocrine gastrin have been demonstrated to stimulate growth of colorectal cancer but it is not known if gastrin affects the growth of colonic polyps. The purpose of this study was to determine if gastrin and C CKBR are expressed in human colonic polyps and to determine at which stage of progression this occurs. Methods-A range of human colonic polyps was assessed for gastrin and CCKBR gene and protein expression. Results-Normal colonic mucosa did not express gastrin or CCKBR. Gastrin and CCKBR reverse transcription polymerase chain reaction products were detect ed and verified by specific hybridisation with an oligo probe on Southern b lots. Gastrin and CCKBR were expressed in 78% and 81% of polyps, respective ly. Both genes were coexpressed in 97% of eases. Immunohistochemistry ident ified progastrin in 91%, glycine extended gastrin 17 in 80%, and amidated g astrin 17 in only 47% of polyps. CCKBR was present in 96% of polyps. Expres sion of gastrin and CCKBR was seen in all histological types and sizes of p olyps. Conclusions-This study is the first to show widespread expression of both g astrin and its receptor in colorectal polyps. Their activation occurs early in the adenoma-carcinoma sequence. Gastrin may promote progression through the adenoma-carcinoma sequence.