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CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia
BACKGROUND: Intestinal metaplasia (IM) is considered a key pivot point in the Correa model of gastric cancer (GC). It is histologically subtyped into the complete and incomplete subtypes, the latter being associated with a greater risk of progression. However, the clinical utility of IM subtyping re...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026694/ https://www.ncbi.nlm.nih.gov/pubmed/35448971 http://dx.doi.org/10.1186/s12876-022-02268-z |
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author | Koulis, Athanasios Di Costanzo, Natasha Mitchell, Catherine Lade, Stephen Goode, David Busuttil, Rita A. Boussioutas, Alex |
author_facet | Koulis, Athanasios Di Costanzo, Natasha Mitchell, Catherine Lade, Stephen Goode, David Busuttil, Rita A. Boussioutas, Alex |
author_sort | Koulis, Athanasios |
collection | PubMed |
description | BACKGROUND: Intestinal metaplasia (IM) is considered a key pivot point in the Correa model of gastric cancer (GC). It is histologically subtyped into the complete and incomplete subtypes, the latter being associated with a greater risk of progression. However, the clinical utility of IM subtyping remains unclear, partially due to the absence of reliable defining biomarkers. METHODS: Based on gene expression data and existing literature, we selected CD10 and Das1 as candidate biomarkers to distinguish complete and incomplete IM glands in tissues from patients without GC (IM-GC) and patients with GC (IM + GC). Immunohistochemical staining of individually subtyped IM glands was scored after blinding by two researchers using tissue belonging to both IM-GC and IM + GC patients. Whole tissue Das1 staining was further assessed using digital image quantification (cellSens Dimension, Olympus). RESULTS: Across both cohorts CD10 stained the IM brush border and was shown to have a high sensitivity (87.5% and 94.9% in IM-GC and IM + GC patients respectively) and specificity (100.0% and 96.7% respectively) with an overall AUROC of 0.944 for complete IM glands. By contrast Das1 stained mainly goblet cells and the apical membrane of epithelial cells, mostly of incomplete IM glands with a low sensitivity (28.6% and 29.3% in IM-GC and IM + GC patients respectively) but high specificity (98.3% and 85.1% respectively) and an overall AUROC of 0.603 for incomplete IM glands. A combined logistic regression model showed a significant increase in AUROC for detecting complete IM glands (0.955 vs 0.970). Whole tissue digital quantification of Das1 staining showed a significant association with incomplete IM compared to complete IM, both in IM-GC and in IM + GC patients (p = 0.016 and p = 0.009 respectively, Mann–Whitney test and unpaired t test used). Additionally, complete IM in IM + GC patients exhibited significantly more Das1 staining than in IM-GC patients (p = 0.019, Mann–Whitney test). CONCLUSIONS: These findings suggest that CD10 is an outstanding biomarker for complete IM and Das1 may be useful as a secondary biomarker for IM glands at greater risk of progression irrespective of IM subtype. Overall, the clinical use of these biomarkers could lead to improved patient stratification and targeted surveillance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-022-02268-z. |
format | Online Article Text |
id | pubmed-9026694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90266942022-04-23 CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia Koulis, Athanasios Di Costanzo, Natasha Mitchell, Catherine Lade, Stephen Goode, David Busuttil, Rita A. Boussioutas, Alex BMC Gastroenterol Research BACKGROUND: Intestinal metaplasia (IM) is considered a key pivot point in the Correa model of gastric cancer (GC). It is histologically subtyped into the complete and incomplete subtypes, the latter being associated with a greater risk of progression. However, the clinical utility of IM subtyping remains unclear, partially due to the absence of reliable defining biomarkers. METHODS: Based on gene expression data and existing literature, we selected CD10 and Das1 as candidate biomarkers to distinguish complete and incomplete IM glands in tissues from patients without GC (IM-GC) and patients with GC (IM + GC). Immunohistochemical staining of individually subtyped IM glands was scored after blinding by two researchers using tissue belonging to both IM-GC and IM + GC patients. Whole tissue Das1 staining was further assessed using digital image quantification (cellSens Dimension, Olympus). RESULTS: Across both cohorts CD10 stained the IM brush border and was shown to have a high sensitivity (87.5% and 94.9% in IM-GC and IM + GC patients respectively) and specificity (100.0% and 96.7% respectively) with an overall AUROC of 0.944 for complete IM glands. By contrast Das1 stained mainly goblet cells and the apical membrane of epithelial cells, mostly of incomplete IM glands with a low sensitivity (28.6% and 29.3% in IM-GC and IM + GC patients respectively) but high specificity (98.3% and 85.1% respectively) and an overall AUROC of 0.603 for incomplete IM glands. A combined logistic regression model showed a significant increase in AUROC for detecting complete IM glands (0.955 vs 0.970). Whole tissue digital quantification of Das1 staining showed a significant association with incomplete IM compared to complete IM, both in IM-GC and in IM + GC patients (p = 0.016 and p = 0.009 respectively, Mann–Whitney test and unpaired t test used). Additionally, complete IM in IM + GC patients exhibited significantly more Das1 staining than in IM-GC patients (p = 0.019, Mann–Whitney test). CONCLUSIONS: These findings suggest that CD10 is an outstanding biomarker for complete IM and Das1 may be useful as a secondary biomarker for IM glands at greater risk of progression irrespective of IM subtype. Overall, the clinical use of these biomarkers could lead to improved patient stratification and targeted surveillance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-022-02268-z. BioMed Central 2022-04-21 /pmc/articles/PMC9026694/ /pubmed/35448971 http://dx.doi.org/10.1186/s12876-022-02268-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Koulis, Athanasios Di Costanzo, Natasha Mitchell, Catherine Lade, Stephen Goode, David Busuttil, Rita A. Boussioutas, Alex CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia |
title | CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia |
title_full | CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia |
title_fullStr | CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia |
title_full_unstemmed | CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia |
title_short | CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia |
title_sort | cd10 and das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026694/ https://www.ncbi.nlm.nih.gov/pubmed/35448971 http://dx.doi.org/10.1186/s12876-022-02268-z |
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