title: Increased expressions of claudin 4 and 7 in atypical adenomatous hyperplasia and adenocarcinoma of the lung.
abstract: Abnormal expression of claudin (Cldn), the main constituent of tight junctions, may play a crucial role in carcinogenesis. To elucidate these abnormalities of tight junctions in lung adenocarcinoma during carcinogenesis, we examined immunohistochemical expressions of Cldn4 and Cldn7 in human lung resection materials. Lung resection specimens from 86 patients were studied, including 16 atypical adenomatous hyperplasia (AAH), 19 adenocarcinoma in situ (AIS), 32 invasive adenocarcinoma (ADC), 5 AIS with AAH, 2 ADC with AAH, 10 ADC with AIS, and 2 ADC with AIS and AAH. The immunohistochemical staining (IHC) score was defined for both the extent and intensity of staining. IHC score for Cldn4 in AIS and ADC was significantly higher than that in alveolar epithelium (AE) and AAH (p < 0.001 for both). In addition, the AAH score was significantly higher than that in AE (p < 0.001). The Cldn7 score in ADC was significantly increased compared with AE and AAH (p < 0.001 for both). These results suggested that increase of Cldn4-expression may be involved in early molecular events during carcinogenesis of adenocarcinoma, whereas increase of Cldn7-expression may be associated with tumor invasion or progression.
authors.affiliation: Department of Respiratory Medicine and Allergology, Sapporo Medical University, School of Medicine, South-1 West-16, Chuo-ku, Sapporo, 060-8543, Japan. gyamada@sapmed.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
authors.affiliation: Department of Pathology, Sapporo Medical University, School of Medicine, South-1 West-17, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Pathology, Sapporo Medical University, School of Medicine, South-1 West-17, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.affiliation: Division of Advanced Medicine Promotion, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Department of Respiratory Medicine and Allergology, Sapporo Medical University, School of Medicine, South-1 West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Pathology, Sapporo Medical University, School of Medicine, South-1 West-17, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
authors.affiliation: Department of Respiratory Medicine and Allergology, Sapporo Medical University, School of Medicine, South-1 West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D062506:Claudin-4 / Q000378:metabolism*; D057167:Claudins / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C473255:CLDN7 protein, human; D062506:Claudin-4; D057167:Claudins
keywords: Adenocarcinoma in situ; Atypical adenomatous hyperplasia; Invasive adenocarcinoma; Tight junction molecule