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.
Introduction The Cdx2 gene provides an intestinal differentiation of epithelial cells and plays an oncosupressive role. An indirect method of the Cdx2 gene expression assessment is the immunohistochemical study of its product, the CDX2 protein. Therefore, the common approach to the immunohistochemical study of the CDX2 protein hasn’t been developed yet. A semi-quantitative CDX2 index based on the percentage of CDX2-positive cells in the tissue specimen, the staining intensity and an expression pattern has been proposed.The purpose of the study was to assess the reproducibility of the semi-quantitative CDX2 index calculation in chronic atrophic gastritis stages I-IV.Materials and methods 20 chronic atrophic gastritis cases (5 cases for each stage of the gastritis according to the Operative link for gastritis assessment system) were taken according to the Maastricht V protocol and examined by the immunohistochemical method (CDX2, clone EPR2764Y, ready to use). The reproducibility of the CDX2 semi-quantitative index was assessed by five pathologists. An agreement between observed raters was measured by the kappa statistics.Results The Cohen’s κ value is 0,8 for unweighted κ and 0,97 for weighted κ (extremely high level of agreement) for the semi-quantitative CDX2 index calculation.Discussion The least reproducible parameter used for the semi-quantitative CDX2 index calculation the percentage of CDX2-positive cells because of the subjective assessment. The Cohen’s weighted κ value was higher compared to the unweighted κ because of the close yet not similar CDX2 semi-quantitative index values calculated by pathologists.Conclusion The semi-quantitative CDX2 index can be used to rank CDX2 expression and has a high level of reproducibility.
Introduction Diagnosis of the gastric mucosa atrophy represents an important problem, the solution of which depends on the possibility of secondary prevention of gastric cancer. A possible way of solution is the use of immunohistochemical markers - proteins associated with cellular remodeling of gastric mucosa, PDCD4 and CDX2.The aim of the work is to evaluate the possibility of using immunohistochemical markers PDCD4 and CDX-2 to diagnose atrophy of the gastric mucosa in chronic gastritis and increase the informative value of biopsy examination.Materials and method The object of the study was 155 cases of biopsy examination of the gastric mucosa of patients with chronic gastritis (5 fragments per case − 775 biopsy specimens). A comparative semi-quantitative assessment of immunohistochemical expression of CDX2, PDCD4 at different stages of chronic gastritis was performed. Spearman correlation coefficient was used to assess correlation relationship.Results There were no statistically significant differences in the level of PDCD4 in studied samples depending on the stage of chronic gastritis, p=0.06. Statistically significant increase of CDX2sum index in progressing stage of chronic atrophic gastritis (p=0.005), demonstrated a pronounced positive correlation r=0.70 (p<0.01).Discussion According to the results obtained, it is shown that the decline in PDCD4 protein does not occur with the progression of atrophy severity. Complementary use of immunohistochemical marker CDX2 is able to give an idea of the presence and severity of both metaplastic and absolute atrophic changes in the gastric mucosa.Conclusion Equally high level of PDCD4 protein index in the gastric mucosa at different stages of chronic gastritis excludes the possibility of its use as an immunohistochemical marker of atrophy. Semi-quantitative immunohistochemical index of CDX2 protein can be used as an additional marker in decision support system for assessment of atrophic changes in gastric mucosa.
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