Objective  To explore the expression of claudin-1, -3, -4, and -7 as well as their clinical pathological significance in the gastric adenocarcinoma in the process of invasion and metastasis.

  Methods  Expression of claudin-1, -3, -4, and -7 were detected in the mucosal adenocarcinoma and adjacent epithelium (including normal gastric or intestinal metaplastic epithelium) as well as the tumor central area. The invasive front and lymph node metastases for 139 cases of gastric cancer were analyzed using tissue microarray and immunohistochemical SP methods.

  Results  Claudin-1, -3, -4, and -7 proteins showed heterogeneous expression in the gastric epithelium, intestinal metaplasia, and gastric adenocarcinoma, localized in the cell membrane and cytoplasm near the edge of the membrane. The expression levels of claudin-1, -3, -4, and -7 in the intestinal metaplastic epithelium were higher than those in the gastric epithelial (P < 0.05). Expression levels of claudin-1 and -7 were downregulated in mucosal adenocarcinoma compared with those in adjacent gastric mucosa or intestinal metaplastic epithelium (P < 0.05). Claudin-1, -3, -4 and -7 expression levels in gastric mucosal adenocarcinoma were negatively associated with tumor histological type (χ² = 10.22, 12.47, 10.85, and 9.28; P < 0.05). Claudin-1, -3, -4, and -7 expression levels changed parabolically during vertical infiltration and metastasis, exhibiting an initial upregulation before an eventual downregulation of expression, with a peak in the tumor center (χ² = 111.84, 52.35, 33.71, and 111.91; P < 0.05). Negative correlation was found between claudin- 1 expression in the tumor center and clinical stages of gastric cancer (χ² = 6.879, P < 0.05). Low expression levels of claudin-1 and -3 in the tumor center were associated with poor prognosis (χ² = 5.530 and χ² = 9.846, P < 0.05). However, only claudin-3 maintained prognostic independence in the multivariate analyses.

  Conclusion  Claudin-1, -3, -4, and -7 expression levels change during invasion and metastasis of gastric adenocarcinoma, which may be related with intestinal metaplasia of gastric mucosa, differentiation, proliferation, and epithelium-mesenchymal transition of stomach adenocarcinoma.