The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer

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...

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Veröffentlicht in:International journal of experimental pathology 2021-06, Vol.102 (3), p.172-178
Hauptverfasser: Armstrong, Gemma R., Khot, Mohammed Ibrahim, Tiernan, Jim P., West, Nick P., Perry, Sarah L., Maisey, Tom I., Hughes, Thomas A., Jayne, David G.
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container_end_page 178
container_issue 3
container_start_page 172
container_title International journal of experimental pathology
container_volume 102
creator Armstrong, Gemma R.
Khot, Mohammed Ibrahim
Tiernan, Jim P.
West, Nick P.
Perry, Sarah L.
Maisey, Tom I.
Hughes, Thomas A.
Jayne, David G.
description 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 = 
doi_str_mv 10.1111/iep.12395
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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 = &lt;.0001). ROC‐AUC analysis of c‐Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P &lt; .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.</description><identifier>ISSN: 0959-9673</identifier><identifier>EISSN: 1365-2613</identifier><identifier>DOI: 10.1111/iep.12395</identifier><identifier>PMID: 33951261</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>biomarker ; Biomarkers ; Cancer ; Cell membranes ; Colorectal cancer ; Colorectal carcinoma ; c‐Met ; Diagnostic systems ; Epithelial cells ; Epithelium ; Immunohistochemistry ; Rank tests ; Tissues</subject><ispartof>International journal of experimental pathology, 2021-06, Vol.102 (3), p.172-178</ispartof><rights>2021 The Authors. published by John Wiley &amp; Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).</rights><rights>2021 The Authors. 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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 = &lt;.0001). ROC‐AUC analysis of c‐Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P &lt; .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%). 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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 = &lt;.0001). ROC‐AUC analysis of c‐Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P &lt; .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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33951261</pmid><doi>10.1111/iep.12395</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8179-8736</orcidid><oa>free_for_read</oa></addata></record>
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subjects biomarker
Biomarkers
Cancer
Cell membranes
Colorectal cancer
Colorectal carcinoma
c‐Met
Diagnostic systems
Epithelial cells
Epithelium
Immunohistochemistry
Rank tests
Tissues
title The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer
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