High gastrin releasing peptide receptor mRNA level is related to tumour dedifferentiation and lymphatic vessel invasion in human colon cancer

The neuropeptide bombesin stimulates tumour cell proliferation in vitro. Th rough pharmacological testing, 20-40% of human colorectal tumours have been shown to be equipped with bombesin/gastrin releasing peptide receptor (GRP -R). The aim of the present study was to test whether GRP-R expression is c orrelated with tumour characteristics and usual prognostic factors in color ectal adenocarcinomas. A sensitive reverse transcription (RT)-competitive p olymerase chain reaction (PCR) method was validated by studying GRP-R mRNA in separated layers of normal colonic wall, and GRP-R mRNA levels (in paral lel with binding studies) in colon cancer cell lines LoVo and Caco-2. GRP-R mRNA levels were then determined in 29 surgical tumour specimens and the r esults compared with tumour histology and, using histochemistry, with the a ccumulation of p53 protein and a Ki-67 cell proliferation index. The mRNA w as not detected in normal colonic epithelium, whereas a distinct signal was observed after amplification in 27/29 (93%) tumour specimens. Estimates of mRNA levels in the 27 positive tumours ranged from 52 to 8000 amol/0.25 mu g total RNA, and were significantly higher in poorly/moderately differenti ated tumours (P < 0.05) and in tumours with lymphatic vessel invasion (P < 0.01). There was no relationship with p53 accumulation or to the proliferat ion index. Our results show that GRP-R mRNA can be detected in most colorec tal tumour specimens, and suggest a link between high mRNA levels and both tumour dedifferentiation and lymph vessel invasion, but not proliferation. (C) 1999 Elsevier Science Ltd. All rights reserved.