Reduced expression of claudin-7 correlates with invasion and metastasis in squamous cell carcinoma of the esophagus

Hum Pathol. 2006 May;37(5):569-77. doi: 10.1016/j.humpath.2005.12.018.


Claudins are transmembrane proteins that seal tight junctions, bind with peripheral protein zonula occludens (ZO)-1, and are known to play an important role in several normal tissues and cancers. However, the role of claudin-1 and claudin-7 expressions in esophageal squamous cell carcinoma remains to be clarified. In the present study, we confirmed the expressions of claudin-1, claudin-7, and ZO-1 in the prickle cell layer of the normal human esophageal squamous epithelium. The expressions of claudin-1 and claudin-7 at the invasive front of the esophageal squamous cell carcinoma were analyzed immunohistochemically to clarify their role in tumor progression. Reduced expression of claudin-7 at the invasive front of the esophageal cancer was significantly associated with the depth of invasion (P = .004), stage (P = .038), lymphatic vessel invasion (P = .001), and lymph node metastasis (P = .014). In contrast, significant association was not detected between claudin-1 expression and clinicopathologic factors except for histologic differentiation of the tumor (P = .0029). Comparison of claudin-7 expression at the invasive front of the primary tumor and its corresponding metastatic lymph nodes revealed significant reduction in claudin-7 expression in the metastatic lymph nodes (P = .007). These results suggest that the reduced expression of claudin-7 at the invasive front of esophageal squamous cell carcinoma may lead to tumor progression and subsequent metastatic events. Thus, claudin-7 can be a novel marker for the prediction of lymph node metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / secondary
  • Claudin-1
  • Claudins
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophagus / metabolism
  • Esophagus / pathology
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness


  • Biomarkers, Tumor
  • CLDN1 protein, human
  • CLDN7 protein, human
  • Claudin-1
  • Claudins
  • Membrane Proteins