CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia
- Author(s)
- Koulis, A; Di Costanzo, N; Mitchell, C; Lade, S; Goode, D; Busuttil, RA; Boussioutas, A;
- Journal Title
- BMC Gastroenterology
- Publication Type
- Research article
- Abstract
- 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.
- Keywords
- Biomarkers; Gastric Mucosa/pathology; Humans; Immunohistochemistry; Metaplasia/pathology; *Precancerous Conditions/pathology; *Stomach Neoplasms/pathology; Cd10; Das1; Digital quantification; Gastric cancer; Gene expression profiling; Intestinal metaplasia subtypes; Logistic regression model; Risk of progression
- Department(s)
- Laboratory Research; Pathology
- PubMed ID
- 35448971
- Publisher's Version
- https://doi.org/10.1186/s12876-022-02268-z
- Open Access at Publisher's Site
https://doi.org/10.1186/s12876-022-02268-z- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-20 05:36:48
Last Modified: 2024-12-20 05:37:53