Institute for the Application of Nuclear Energy - INEP, University of Belgrade, Belgrade-Zemun, Serbia.
Center for Endocrine Surgery, Institute for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia.
Int J Exp Pathol. 2018 Apr;99(2):87-94. doi: 10.1111/iep.12268. Epub 2018 Apr 17.
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 (P < 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.
表皮生长因子受体（EGFR）及其下游效应物黏着斑激酶（FAK）在人类恶性肿瘤中常过度表达，并与肿瘤侵袭性有关。我们旨在研究 EGFR 和 FAK 的表达与甲状腺乳头状癌（PTC）患者临床表型之间的关系。采用免疫组织化学和 Western blot 分析了 104 例 PTC 组织样本中 EGFR 和 FAK 的表达谱。此外，对 20 例原发性肿瘤及其淋巴结转移灶进行了 EGFR 和 FAK 的免疫组织化学分析。结果发现，EGFR 和 FAK 的高表达率分别为 55.77%和 57.69%，两者之间存在强烈的正相关（P<0.0001，Spearman 相关系数=0.844）。两种分子的表达及其共表达与淋巴结转移（LNM）、肿瘤浸润程度、甲状腺外侵犯和患者的 pT 分期显著相关。Western blot 分析证实，EGFR 和 FAK 高水平的共表达与不良的临床病理特征相关。与相应的原发性肿瘤相比，在 LNM 中发现 EGFR 和 FAK 的水平升高或维持较高水平，表明它们在淋巴扩散过程中的表达一致。综上所述，EGFR 及其下游效应物 FAK 的高水平与淋巴扩散和肿瘤浸润有关，提示它们参与了 PTC 的进展，并表明这两种分子可能预测其侵袭性行为。此外，FAK 可能成为晚期甲状腺癌患者抗癌治疗的潜在靶点。
