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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND
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.
AIM
To comprehensively define c-MET expression in sporadic and IBD-associated colorectal carcinogenesis.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Original languageEnglish
JournalWorld Journal of Gastroenterology
Early online date27 Feb 2022
DOIs
Publication statusE-pub ahead of print - 27 Feb 2022

Keywords

  • Inflammatory bowel diseases
  • Colorectal cancer
  • Surveillance
  • Detection
  • c-MET
  • Immunohistochemistry

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