E-cadherin/α-catenin deregulated co-expression in thyroid carcinoma based on tissue microarray digital image analysis

Purpose: Deregulation of cell-to-cell adhesion molecules is a common and also critical genetic event in epithelial malignancies leading to an increasing metastatic potential. Among them, e-cadherin and catenins especially a and beta-, act as oncogenes during the carcinogenetic process affecting specific signaling transduction pathways (i.e. Wnt/b-catenin). Concerning thyroid carcinoma, decreased or loss of expression in these proteins seems to affect the biological behavior of the neoplasm increasing its aggressiveness. The aim of this study was to investigate the deregulation of e-cadherin/a-catenin complex in thyroid carcinomas. Methods: Thirty-five paraffin-embedded tissue samples including thyroid carcinomas (N=20) and also 15 cases of benign follicular nodules were cored at 1 mm diameter and transferred to a microarray block. Immunohistochemistry (IHC) was performed using anti- e-cadherin/a-catenin antibodies. Digital image analysis was also implemented for measuring the corresponding protein expression levels. Results: E-cadherin/a-catenin protein expression demon strated a significant progressive decrease regarding benign and malignant lesions (p=0.001). Simultaneous e-cadherin/a-catenin reduced or loss of expression was observed in 10/20 (50%) cancer cases correlated to advanced stage (especially nodal metastasis) of the examined tumours (p=0.02). Concerning the histological type, combined loss of e-cadherin/a-catenin expression was predominantly associated with follicular and anaplastic histology (p=0.001). Interestingly, a-catenin protein expression pattern was significantly correlated with the grade of differentiation of the examined malignancies (p=0.01). Conclusions: Progressive loss of e-cadherin mainly and also a-catenin expression is associated with an aggressive phenotype (low differentiation, increased metastatic activity/advanced stage) in thyroid carcinomas. Based on their aberrant protein expression, novel agents have been developed for restoring their normal function.