Published online Apr 7, 2022. doi: 10.3748/wjg.v28.i13.1338
Peer-review started: November 23, 2021
First decision: January 8, 2022
Revised: January 17, 2022
Accepted: February 27, 2022
Article in press: February 27, 2022
Published online: April 7, 2022
Patients with inflammatory bowel disease (IBD) are more likely to develop colorectal cancer (CRC) compared with the general population, and surveillance colonoscopy is therefore performed at defined intervals to identify pre-malignant lesions. Despite this, IBD post-colonoscopy CRC rates remain unacceptably high. One key challenge is endoscopically identifying the more subtle and flat lesions associated with dysplasia and cancer in IBD.
There is an urgent need to improve endoscopic detection of pre-malignant lesions, especially in patients with IBD. Recent studies have suggested that an intravenously administered fluorescent probe against c-MET protein may improve the detection of sporadic colorectal lesions-specifically small non-polypoid lesions of similar morphology to IBD-associated (pre-) malignant lesions. However, most data come from murine studies or sporadic disease, and there are lack of immunohistochemical data defining c-MET expression in IBD-associated colonic lesions. This is limiting translational studies.
This study was designed to systematically assess the immunohistochemical expression of c-MET in both sporadic and inflammatory bowel disease-associated colonic lesions.
c-MET expression intensity was semi-quantitatively assessed after immunohistochemically staining formalin-fixed paraffin-embedded tissue specimens with an anti-c-MET antibody. Tissue had been colonoscopically or surgically retrieved from patients with and without IBD between 1994-2017, and included normal colonic mucosa, hyperplastic polyps, sessile serrated lesions, tubular/tubulovillous adenomas with low or high grade dysplasia, sporadic-CRC, quiescent IBD mucosa, inflamed IBD mucosa, IBD-associated dysplastic lesions, and IBD-associated CRC.
There was ubiquitous expression of c-MET in normal colonic mucosa, as well as in sporadic and IBD lesions. c-MET expression intensity was similar between low vs high grade dysplasia, and between hyperplastic polyps vs sessile serrated lesions. However, c-MET expression was stronger in sporadic dysplasia and cancer compared with normal colonic mucosa. Similarly, c-MET expression was stronger in IBD-associated dysplastic and malignant lesions compared with quiescent IBD mucosa. There was no difference in c-MET expression between inflamed IBD mucosa and IBD-associated dysplasia or malignant lesions.
c-MET expression intensity is stronger in dysplastic and malignant lesions compared with normal colonic epithelium and quiescent IBD mucosa. These data provide a platform to allow future studies to investigate whether an intravenous anti-c-MET probe could help endoscopically identify dysplasia and malignancy, particularly within surveillance colonoscopy programmes for IBD patients where post-colonoscopy CRC rates are unacceptably high.
Further study is needed to determine whether histopathological expression correlates with mucosal expression at endoscopy in the context of IBD. The ability of such a probe to improve the endoscopic detection of colorectal lesions and reduce the post-colonoscopy CRC rate should then be assessed, in patients with quiescent IBD.