title: Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in thyroid neoplasms.
abstract: Claudins and occludin are integral constituents of tight junctions and are deregulated in a variety of malignancies. Their role in thyroid carcinogenesis has not yet been elucidated. This study investigates the expression of occludin and claudin-1, -4 and -7 in thyroid neoplasms. Ninety-one thyroid neoplasms (15 follicular adenomas, 15 follicular carcinomas, 26 papillary carcinomas, 16 papillary microcarcinomas, 8 medullary carcinomas, 3 poorly differentiated carcinomas, 8 undifferentiated carcinomas) were immunostained with antibodies against occludin and claudin-1, -4 and -7. Occludin was mainly expressed in the form of intracytoplasmic vesicles, whereas all claudins tested exhibited membranous immunostaining. Thirteen out of 15 follicular adenomas, 10/15 follicular carcinomas, 24/26 papillary carcinomas, 15/16 papillary microcarcinomas, 1/8 medullary carcinomas, 2/3 poorly differentiated carcinomas and 2/8 undifferentiated carcinomas exhibited claudin-1 expression, whereas claudin-4 was expressed in 13/15, 12/15, 23/26, 13/16, 7/8, 2/3 and 2/8 of the tumors, respectively, and claudin-7 expression was found in 67, 33, 73, 69, 25, 0 and 13% of the cases, respectively. Occludin was expressed in 100% follicular adenomas, 80% follicular carcinomas, 96% papillary carcinomas, 50% papillary microcarcinomas, 50% medullary carcinomas, 33% poorly differentiated carcinomas and 88% undifferentiated carcinomas. Occludin expression was reduced in papillary microcarcinomas, medullary carcinomas and poorly differentiated carcinomas. All claudins exhibited reduced expression in undifferentiated carcinomas. Claudin-1 was additionally reduced in medullary carcinomas and claudin-7 in follicular, medullary and poorly differentiated carcinomas. A correlation between loss of claudin-1 expression and worse disease-free survival was noted on univariate analysis. Dedifferentiation of the thyroid carcinomas is accompanied by reduction in claudin-1, -4 and -7 expression. A differential expression of tight junction proteins in the different histologic types of thyroid gland is noted. Additionally, claudin-1 expression may be an important prognostic indicator of recurrence in thyroid carcinomas.
authors.affiliation: Faculty of Medicine, Department of Pathology, University Hospital, University of Patras, Patras, Greece.
authors.forename: Vassiliki N
authors.initials: VN
authors.lastname: Tzelepi
authors.forename: Athanassios C
authors.initials: AC
authors.lastname: Tsamandas
authors.forename: Helen D
authors.initials: HD
authors.lastname: Vlotinou
authors.forename: Constantine E
authors.initials: CE
authors.lastname: Vagianos
authors.forename: Chrisoula D
authors.initials: CD
authors.lastname: Scopa
mesh_terms: D000236:Adenoma / Q000737:chemistry; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018276:Carcinoma, Medullary / Q000737:chemistry; D002291:Carcinoma, Papillary / Q000737:chemistry; D002454:Cell Differentiation; D062445:Claudin-1; D062506:Claudin-4; D057167:Claudins; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D062793:Occludin; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D019108:Tight Junctions / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C568157:CLDN4 protein, human; C473255:CLDN7 protein, human; D062445:Claudin-1; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin