Related Experiment Video
Updated: Jul 10, 2026
An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in
Vassiliki N Tzelepi1, Athanassios C Tsamandas, Helen D Vlotinou
1Faculty of Medicine, Department of Pathology, University Hospital, University of Patras, Patras, Greece.
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.
Insights
Tight junction proteins claudins and occludin are altered in thyroid cancer. Reduced claudin-1 expression correlates with worse disease-free survival, suggesting its prognostic value in thyroid neoplasms.
Area of Science:
- Oncology
- Cell Biology
- Molecular Pathology
Background:
- Tight junctions, crucial for epithelial barriers, involve proteins like claudins and occludin.
- Dysregulation of these proteins is observed in various cancers.
- The specific role of tight junction proteins in thyroid carcinogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the expression patterns of occludin and claudins (1, 4, and 7) in a diverse range of thyroid neoplasms.
- To determine if alterations in these tight junction proteins correlate with specific thyroid tumor types or dedifferentiation.
- To assess the potential of claudin-1 as a prognostic marker for thyroid carcinoma recurrence.
Main Methods:
- Immunohistochemical staining was performed on 91 thyroid neoplasms, including adenomas and various carcinoma subtypes.
- Antibodies against occludin and claudins-1, -4, and -7 were used to evaluate protein expression.
- Expression levels were analyzed across different histological types and correlated with clinical outcomes, including disease-free survival.
Main Results:
- Occludin showed predominantly intracytoplasmic localization, while claudins displayed membranous staining.
- Claudin-1, -4, and -7 expression decreased with increasing tumor dedifferentiation, particularly in undifferentiated carcinomas.
- Reduced expression of occludin was noted in papillary microcarcinomas and medullary carcinomas; claudin-1 was reduced in medullary carcinomas; claudin-7 was reduced in follicular, medullary, and poorly differentiated carcinomas.
- Loss of claudin-1 expression was associated with worse disease-free survival on univariate analysis.
Conclusions:
- Thyroid carcinogenesis involves differential expression and reduction of tight junction proteins, including claudins and occludin.
- Dedifferentiation of thyroid carcinomas is characterized by a decrease in claudin-1, -4, and -7 expression.
- Claudin-1 expression may serve as a significant prognostic indicator for recurrence in thyroid carcinomas.
Related Concept Videos
01:29Tight Junctions
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
01:23The Thyroid Gland
The follicles have a central cavity lined by simple cuboidal to squamous epithelial cells called follicular cells. These cells produce the glycoprotein...
01:27Hyperthyroidism II: Pathophysiology
01:19Cadherins in Tissue Organization
Cell Sorting During Development
Cell sorting plays an...
01:20Classification of Epithelial Tissues: Glandular Epithelium
Multicellular glands are formed during early development when epithelial budding...