Armstrong, GR, Khot, MI orcid.org/0000-0002-5062-2284, Tiernan, JP et al. (5 more authors) (2021) The utility of c-Met as a diagnostic tissue biomarker in primary colorectal cancer. International Journal of Experimental Pathology, 102 (3). pp. 172-178. ISSN 0959-9673
Abstract
The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial.
Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c-Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi-quantifiable score, and differences in median scores analysed using the Wilcoxon signed-rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c-Met as a biomarker in CRC.
Epithelial cell membrane expression of c-Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6-15) versus median 6.00 (IQR 2.70-12.00) respectively (P = <.0001). ROC-AUC analysis of c-Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%-89.45%) but sensitivity of only 30.92% (CI 25.37%-36.90%).
Thus c-Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c-Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. International Journal of Experimental Pathology published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | biomarker; c-Met; colorectal cancer; immunohistochemistry |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) > Trans Anaesthetics & Surgical Sciences (Leeds) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L386 |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Mar 2021 16:14 |
Last Modified: | 25 Jun 2023 22:35 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/iep.12395 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171626 |