Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2022; 28(13): 1338-1346
Published online Apr 7, 2022. doi: 10.3748/wjg.v28.i13.1338
c-MET immunohistochemical expression in sporadic and inflammatory bowel disease associated lesions
Grant Halliday, Ross J Porter, Catherine J Black, Mark J Arends, Shahida Din
Grant Halliday, Catherine J Black, Department of Pathology, Western General Hospital, NHS Lothian, Scotland EH4 2XU, United Kingdom
Ross J Porter, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
Ross J Porter, Shahida Din, Edinburgh Inflammatory Bowel Disease Unit, Western General Hospital, NHS Lothian, Edinburgh EH4 2XU, United Kingdom
Mark J Arends, Cancer Research UK Edinburgh Centre, Institute of Cancer & Genetics, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom
Author contributions: Porter RJ and Halliday G contributed equally to this work; Porter RJ analysed data, wrote the first draft of the manuscript and reviewed and edited the final manuscript; Halliday G performed experiments, contributed to writing the first manuscript draft and reviewed and edited the manuscript; Arends MJ and Black CJ provided histopathological expertise, contributed to study design, performed experiments and reviewed and edited the final manuscript; Din S was the principal investigator for this study, conceptualised and designed the study, analyzed data and reviewed and edited the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: Ethical approval was obtained from Lothian NRS Bioresource Research Tissue Bank (15/ES/0094; SR148, SR389, SR400 and SR588).
Conflict-of-interest statement: Funding bodies did not have any contribution/ influence towards study design, data collection, analysis or interpretation, or writing or submission of this manuscript. Din S acknowledges the financial support of NHS Research Scotland (NRS), through NHS Lothian. Porter RJ, Halliday G, Arends MJ and Black CJ do not have any conflicts of interest or disclosures to declare.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Shahida Din, BSc, FRCP, MBChB, PhD, Consultant Physician-Scientist, Edinburgh Inflammatory Bowel Disease Unit, Western General Hospital, NHS Lothian, Anne Feguson Building, Edinburgh EH4 2XU, United Kingdom.
Received: November 23, 2021
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
Research background

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.

Research motivation

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.

Research objectives

This study was designed to systematically assess the immunohistochemical expression of c-MET in both sporadic and inflammatory bowel disease-associated colonic lesions.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.