Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in thyroid neoplasms

• Published in: Modern pathology 2008, Vol.21 (1), p.22-30
• Main Authors: Tzelepi, Vassiliki N, Tsamandas, Athanassios C, Vlotinou, Helen D, Vagianos, Constantine E, Scopa, Chrisoula D
• Format: Article
• Language: English
• Subjects: Adenoma - chemistry; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Cancer; Carcinoma, Medullary - chemistry; Carcinoma, Papillary - chemistry; Cell Differentiation; Claudin-1; Claudin-4; Claudins; Disease-Free Survival; Down-Regulation; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Laboratory Medicine; Male; Medicine; Medicine & Public Health; Membrane Proteins - analysis; Middle Aged; Occludin; original-article; Pathology; Proteins; Thyroid gland; Thyroid Neoplasms - chemistry; Thyroid Neoplasms - mortality; Thyroid Neoplasms - pathology; Thyroid Neoplasms - therapy; Tight Junctions - chemistry; Treatment Outcome; Tumors
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3800959

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.