Expression of Cdx2 and Claudin-2 in the Multistage Tissue of Gastric Carcinogenesis

Abstract

In this paper, we investigated Cdx2 and claudin-2 expression in pathological paraffin tissues of sinus ventriculi from gastroscopic biopsy to determine the correlation between the expressions of these 2 genes during gastric carcinogenesis by immunochemical ABC technique. Altogether, we analyzed 108 chronic superficial gastritis, 55 chronic atrophic gastritis, 109 intestinal-type metaplasia, 93 dysplasia and 52 gastric intestinal-type adenocarcinoma samples. Our results indicated that the percentage of Cdx2-positive cases was 0% (0/108) for chronic superficial gastritis, 0% (0/55) for chronic atrophic gastritis, 90.83% (99/109) for intestinal-type metaplasia, 51.61% (48/93) for dysplasia and 61.54% (32/52) for gastric intestinal-type adenocarcinoma, primarily expressed in the cell nucleus and partly in the cytoplasm (p < 0.05); interestingly, the percentage for the intestine-type metaplasia was markedly high. The percentage of claudin-2-positive cases was 0% (0/108) for chronic superficial gastritis, 0% (0/55) for chronic atrophic gastritis, 0% (0/109) for intestinal-type metaplasia, 35.48% (33/93) for dysplasia and 71.15% (37/52) for gastric intestinal-type adenocarcinoma, primarily in the cell membrane and gradually increased in the multistage process of gastric carcinogenesis (p < 0.05). Significant correlations were found between claudin-2 and Cdx2 protein expression in dysplasia and intestine-type adenocarcinoma (r = 0.112, p < 0.05). Thus, there may be a correlation between the expression of claudin-2 and Cdx2 in stages of dysplasia and cancer.

The Expression of Claudin-1, Claudin-2, Claudin-3, and Claudin-4 in Gastric Cancer Tissue

“…However, expression of claudin family proteins has been rarely reported, and outcomes have been limited to evaluation of one or two claudin proteins. Furthermore, the expression of claudin has been reported for numerous types of malignancies such as for the breast, pancreas, liver, and esophagus in previous studies [10][11][12][13][14][15]. Claudins, however, could be clinically considered as feasible molecular markers for targeting of progression or metastasis in gastric cancer.…”

“…Expression of claudin-1 is related to a poor prognosis in colon cancer and increased re-expression during apoptosis of breast cancer cells [10,11]. Claudin-2 has a potential barrier function within gastrointestinal organs and expression is related to gastric adenocarcinoma [12,13]. Claudin-3 and claudin-4, previously classified as intestinal claudin phenotypes, have an important role in the metastatic pathway [14].…”

Aberrant expression of intelectin-1 in gastric cancer: its relationship with clinicopathological features and prognosis

“…Through the analysis of human ITLN-1 promoter with the online software Genomatix (http://www.genomatix.de), we found four potential binding sites for transcription factor CDX2, a member of the caudal-related homeobox gene family that plays a critical role in the regulation of intestine-speciWc gene expression (Drummond et al 1996;Yamamoto et al 2003). It has been well established that CDX2 participates in the pathogenesis of intestinal metaplasia and gastric cancer (Eda et al 2002;Park et al 2009;Xin et al 2007). In this study, we demonstrated our hypothesis that there was positive correlation between the expression of CDX2 and ITLN-1 in gastric cancer.…”

Claudin-4 expression in gastric cancer cells enhances the invasion and is associated with the increased level of matrix metalloproteinase-2 and -9 expression

“…Using cDNA microarray and immunohistochemistry analysis, our previous studies have shown that the expression of claudin-4 is significantly higher in intestinal-type than in diffuse-type gastric cancer (9,10). Other previous studies have also shown that claudin-2 expression gradually increases in the multistage process of gastric carcinogenesis (11,12). In addition, several other previous studies have reported aberrant claudin expression in various types of cancer.…”