Claudins 1, 3, 4, 5 and 7 in esophageal cancer: loss of claudin 3 and 4 expression is associated with metastatic behavior.

The aim of the study was to elucidate the significance of claudins in surgically treated esophageal carcinoma. The expression of claudins 1, 3, 4, 5 and 7 was studied by immunohistochemistry. Tumor proliferation was assessed with Ki67 immunostaining and apoptosis by the TUNEL method and immunostaining of fragmented caspase 3. Adenocarcinomas showed significantly more cases with moderate or strong claudin 3 (p<0.001) and claudin 5 positivity (p=0.031) compared to squamous cell carcinomas. Loss of claudin 3 expression was associated with the presence of distant metastases (p=0.039). Claudins 3, 4 and 7 had a significant association with either a high apoptotic index or a high number of caspase 3-positive cells, while claudin 5 was associated with increased proliferation. In esophageal carcinoma, claudin expression may vary along with the histology of the tumor. Claudin expression may also be associated with apoptosis or proliferation, suggesting that claudins may contribute to tumor behavior and growth.