CDX₂ Protein as a Surrogate Marker of Gastric Mucosal Atrophy

Abstract

The aim of the study is to develop an approach to assess the severity of the gastric mucosa (GM) atrophy based on the immunohistochemical (IHC) technique to improve diagnostic quality of the stage of chronic gastritis (CG) and to implement predictive assessment of risk factors of gastric cancer development.Material and methods. The study included 155 cases of CG selected in accordance with Operational Link for Gastritis Assessment (OLGA)-system (2 samples of antral gastric mucosa (GM), 1 sample of angular GM and 2 samples of corpus GM). All biopsy samples were examined using histological and IHC (CDX2) techniques. An expression semi-quantitative index was developed to characterize CDX2. The results obtained were statistically processed using the Mann-Whitney and Kruskal-Wallis tests, the Spearman correlation coefficient, and the construction of logistic regression models.Results. It was found that the value of the CDX2 index assessed within the GM biopsy samples positively correlates with the gradation of atrophy (r=0.665 (p<0.001)). A positive correlation remains between the CDX2sum index, calculated by summing the CDX2 index values at each of the GM points, and the stage of chronic gastritis according to the OLGA classification (r=0.70 (p<0.01)). When assessing the contribution of changes at each point of biopsy sampling and retrospective correlation of the CDX2 index at two points of the GM and the stage of chronic gastritis, the greatest correlation was found for points 3 (stomach angle) and 5 (greater curvature of the gastric body), at three points – for points 1 (greater curvature antrum), 3 and 5 (r=0.592 (p<0.01)). Logistic regression models were built to predict the stage of chronic gastritis based on the CDX2 index in the specified combinations of points. The following model was chosen as the optimal one: to take biopsies at three points (1, 3, 5) and assess their CDX2 index, with sensitivity equal 80.4%, specificity equal 82.8% and diagnostic accuracy equal 83.9%.Conclusion. The CDX2 semi-quantitative index can be used to evaluate GM atrophy. The performed regression analysis demonstrates its predictive role. The constructed regression model based on the CDX2 semi-quantitative index calculation at two/three points of GM allows increasing predictive value of biopsy investigations and accuracy of stratified assessment of the gastric adenocarcinoma risk development in patients with CG.