Immunophenotypic Changes during Gastric Carcinogenesis: Expression Patterns of CDX2, SOX2, Ki67, and p53 in Gastric Precancerous Lesions and Adenocarcinoma
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Gastric carcinogenesis is a multistep process characterized by progressive morphological and molecular changes that progress from chronic gastric injury to invasive adenocarcinoma. Identification of biomarkers associated with lesion progression may improve risk stratification and early diagnosis.
The aim of the study was to examine the immunohistochemical expression patterns of CDX2, SOX2, Ki67, and p53 across the spectrum of gastric carcinogenesis and to assess their association with disease progression.
A retrospective cohort study was conducted on 68 formalin-fixed, paraffin-embedded gastric tissue specimens, including normal gastric mucosa, chronic atrophic gastritis, enteric metaplasia complete, enteric metaplasia incomplete, low-grade dysplasia, high-grade dysplasia, intestinal-type gastric adenocarcinoma, and diffuse-type gastric adenocarcinoma. Immunohistochemical staining for CDX2, SOX2, Ki67, and p53 was performed. Expression patterns were evaluated and correlated with lesion severity. The results of the study showed that CDX2 expression significantly increased during the transition from normal gastric mucosa to intestinal metaplasia and dysplasia, reflecting progressive intestinal differentiation. SOX2 expression, on the other hand, showed a gradual decrease, indicating a loss of the gastric epithelial phenotype. Ki67 proliferative activity progressively increased from non-neoplastic lesions to invasive carcinomas. Aberrant expression patterns of p53 expression were predominantly observed in dysplastic lesions and adenocarcinomas. Incomplete intestinal metaplasia showed immunophenotypic features intermediate between complete intestinal metaplasia and dysplasia, confirming its malignant potential. Gastric carcinogenesis is accompanied by progressive changes in epithelial differentiation, proliferative activity, and p53 status. Combined assessment of CDX2, SOX2, Ki67, and p53 may provide valuable information for evaluating gastric precursor lesions and identifying lesions at increased risk of progression to gastric adenocarcinoma.
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