title: Reduced expression of claudin-7 correlates with invasion and metastasis in squamous cell carcinoma of the esophagus.
abstract: 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.
authors.affiliation: Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University, Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Usami
authors.forename: Hideki
authors.initials: H
authors.lastname: Chiba
authors.forename: Fumihito
authors.initials: F
authors.lastname: Nakayama
authors.forename: Junya
authors.initials: J
authors.lastname: Ueda
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
authors.forename: Takahide
authors.initials: T
authors.lastname: Komori
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokozaki
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000556:secondary; D062445:Claudin-1; D057167:Claudins; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C473255:CLDN7 protein, human; D062445:Claudin-1; D057167:Claudins; D008565:Membrane Proteins