Expression of claudin-3 and claudin-4 in gastric adenocarcinomas and precursor lesions

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Claudins are transmembranous tetraspan proteins consisting of ∼27 subtypes. These proteins are essential for the formation of tight junctions that maintain the polarity of epithelial cells. It has been established that claudin proteins are abnormally expressed in a variety of malignancies, including gastric cancer. In this study, we aimed to evaluate the expression pattern of claudin-3 and claudin-4 proteins in a number of Egyptian patients with gastric adenocarcinomas to evaluate the possibility of the use of these claudins as diagnostic markers for the differential diagnosis of gastric carcinoma and to correlate their expression with clinicopathological variables.

Materials and methods

Immunohistochemistry was used to analyze the expression of claudin-3 and claudin-4 in 50 gastric adenocarcinomas and adjacent normal mucosa and precursor lesions. Statistical analysis was used to evaluate the relationship between claudin-3 and claudin-4 expression and various clinicopathological variables.


Normal and inflammatory mucosa was stained focally and weakly for both claudins. In contrast, 90 and 80% of the intestinal metaplasia lesions for claudin-3 and claudin-4, respectively, exhibited moderate to high expression levels. High expression levels in both cytoplasm and membrane were detected in 100% of gastric epithelial dysplastic lesions for both claudins.Claudin-3 and claudin-4 were expressed in 56 and 50% of the gastric cancer tissues, respectively. The expression of claudin-3 and claudin-4 was significantly higher in cases with intestinal-type adenocarcinoma as opposed to the diffuse or mixed subtypes of gastric cancer (P=0.013 and 0.022 for claudin-3 and claudin-4, respectively). Reduced claudin-3 and claudin-4 expression was significantly correlated with lymphatic invasion (P=0.014 and 0.009 for claudin-3 and claudin-4, respectively). Significant positive correlation was found between claudin-3 and claudin-4 expression [Spearman’s correlation (r)=0.886, P=0.000].


Upregulation of claudin-3 and claudin-4 expression during gastric carcinogenesis suggests their potential utility as diagnostic and prognostic molecular markers.

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