Basic Study
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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

Post-colonoscopy colorectal cancer (CRC) rates for patients with inflammatory bowel disease (IBD) are unacceptably high. During colonoscopy, an intravenous fluorescent anti-c-MET probe may improve endoscopic detection of lesions. However, c-MET expression in IBD lesions is poorly defined, limiting translational studies.


To comprehensively define c-MET expression in sporadic and IBD-associated colorectal carcinogenesis.


c-MET expression was immunohistochemically assessed in 319 formalin-fixed paraffin-embedded tissue specimens, colonoscopically or surgically retrieved between 1994-2017. Tissue included: 30 normal colorectal biopsies, 30 hyperplastic polyps (HP), 31 sessile serrated lesions (SSL), 55 tubular/tubulovillous adenomas with low (TA-LGD, n = 32) or high grade dysplasia (TA-HGD, n = 23), 26 sporadic (s)-CRCs, 16 quiescent IBD biopsies, 11 active/inflamed IBD biopsies, 18 IBD-associated dysplastic lesions (IBD-dys), and 102 IBD-CRCs. Expression was scored by two independent observers as: 0 = absent, 1 = weak, 2 = moderate or 3 = strong. Mann-Whitney U and Kruskal-Wallis tests were used to assess significance.


Positive epithelial cytoplasmic and membranous c-MET expression was observed in all tissues, indicating there is ubiquitous expression in the colorectum. c-MET expression was weak in normal colonic epithelium compared with each of the sporadic colonic lesions, including TA-LGD (P < 0.001), TA-HGD (P = 0.004), HP (P < 0.001), SSL (P < 0.001), and s-CRC (P < 0.001). Specifically, in sporadic (non-IBD) lesions, expression was stronger in TA-LGD compared with normal mucosa (P < 0.001), and stronger in s-CRC compared with TA-HGD (P = 0.004). However, there was no significant difference between TA-LGD and TA-HGD (P = 0.852). Further, there was no difference in c-MET expression between HP and SSL (P = 0.065). In IBD, expression was weaker in quiescent colonic mucosa compared with inflamed colonic mucosa (P < 0.001). There was no difference between inflamed colonic mucosa and IBD-dys (P = 0.512) or IBD-CRC (P = 0.296). However, expression was stronger in IBD-dys (P < 0.001) and IBD-CRC (P < 0.001) compared with quiescent IBD colonic mucosa.


The characterisation of c-MET expression suggest that an intravenous probe may improve the endoscopic detection of lesions in both non-IBD patients and IBD patients with quiescent disease.

Keywords: Inflammatory bowel diseases, Colorectal cancer, Surveillance, Detection, c-MET, Immunohistochemistry

Core Tip: During colonoscopy, an intravenous fluorescent anti-c-MET probe may improve endoscopic detection of dysplasia and cancer. However, c-MET expression in inflammatory bowel disease (IBD) lesions is poorly defined, limiting translational studies. We demonstrate that stronger immunohistochemical c-MET expression is associated with dysplasia and cancer in both sporadic and IBD-associated lesions. Therefore, c-MET expression could be exploited clinically to enhance endoscopic detection of pre-malignant lesions and cancer, particularly in IBD where post-colonoscopy colorectal cancer rates are unacceptably high.