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Overexpression of epidermal growth factor receptor and its downstream effector,focal adhesion kinase,correlates with papillary thyroid carcinoma progression
Authors:Sonja Šelemetjev  Aleksandar Bartolome  Tijana Išić Denčić  Ilona Đorić  Ivan Paunović  Svetislav Tatić  Dubravka Cvejić
Institution:1. Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Belgrade‐Zemun, Serbia;2. Center for Endocrine Surgery, Institute for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia;3. Medical Faculty, Institute of Pathology, University of Belgrade, Belgrade, Serbia
Abstract:Epidermal growth factor receptor (EGFR) and its downstream effector, focal adhesion kinase (FAK), have been shown to be overexpressed frequently in human malignancies and implicated in tumour aggressiveness. We aimed to investigate the relationship between EGFR and FAK expression and their possible correlation with the clinical phenotype of patients with papillary thyroid carcinoma (PTC). Expression profiles of EGFR and FAK were analysed in PTC tissue samples (n = 104) by immunohistochemistry and Western blotting. Additionally, EGFR and FAK were immunohistochemically analysed in 20 primary tumours paired with their metastatic tissue in lymph nodes. High expression of EGFR and FAK was found in 55.77% and 57.69% cases, respectively, with a strong positive association between them (< 0.0001, Spearman's correlation coefficient = 0.844). Expression of each molecule and their coexpression correlated significantly with the presence of lymph node metastasis (LNM), degree of tumour infiltration, extrathyroid invasion and pT status of the patients. Western blot analysis confirmed that coexpression of high levels of EGFR and FAK correlated with adverse clinicopathological features. When compared to the corresponding primary tumour, increased or maintained high levels of EGFR and FAK were found in LNM, indicating their concordant expression during lymphatic spread. In conclusion, high levels of EGFR and its downstream effector, FAK, in association with lymphatic spread and tumour infiltration indicate their involvement in PTC progression and suggest that both molecules may predict its aggressive behaviour. Furthermore, FAK could be a potential target for anticancer therapy in patients with advanced thyroid cancer.
Keywords:epidermal growth factor receptor  focal adhesion kinase  papillary thyroid carcinoma  predictive markers  tumour progression
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