Mohamad Pakarul Razy Nur Hidayati, Wan Abdul Rahman Wan Faiziah, Win Thin Thin
Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. Email:
Asian Pac J Cancer Prev. 2019 Jan 25;20(1):277-282. doi: 10.31557/APJCP.2019.20.1.277.
Introduction: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in thyroid cancer. VEGF is known to have high affinity to VEGF receptors such as VEGFR-1 (Flt-1) and VEGFR-2 (KDR). Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and studies showed the increasing incidence of PTC arising in nodular hyperplasia. Targeted therapy on these growth factors and receptors are used in management of both differentiated and undifferentiated thyroid carcinoma. This study aims to determine the expression of VEGF and VEGF receptors (VEGFR) in thyroid nodular hyperplasia and PTC. Methods: A cross-sectional study based on paraffinized archival tissue blocks of 113 nodular hyperplasias and 67 PTC from the thyroidectomy specimens in the year of 2003 to 2014. The tissue sections were then stained by immunohistochemistry for VEGF, VEGFR-1 and VEGFR-2. The lymph node involvement and extrathyroid extension also were determined. Results: The mean age of PTC patients was 44.7±15.8 years and nodular hyperplasia were 42.2±13.6 years. There was a statistical difference of VEGFR-1 (p=0.028) and VEGFR-2 (p=0.003) expression between nodular hyperplasia and PTC. However, no significant difference of VEGF expression (p=0.576) between both diseases. Co-expression of VEGF and VEGFR-1 was significant in both nodular hyperplasia (p=0.016) and PTC (p=0.03), meanwhile no relevant relationship for VEGF and VEGFR-2 expression (p>0.05). No significant association (p>0.05) between lymph node status and extrathyroid extension with age groups, gender, VEGF and VEGFR expression. Conclusions: VEGF, VEGFR-1 and VEGFR-2 showed overexpression in both nodular hyperplasia and PTC. The expression of VEGFR-1 and VEGFR-2 are more significant in PTC with relevant co-expression of VEGF and VEGFR-1. Therefore, the inhibition of VEGFR offers a promising prospect for tumour management in thyroid carcinoma.
血管内皮生长因子(VEGF)是一种血管生成因子,在甲状腺癌中起重要作用。已知VEGF对VEGF受体如VEGFR-1(Flt-1)和VEGFR-2(KDR)具有高亲和力。甲状腺乳头状癌(PTC)是最常见的甲状腺癌,研究表明在结节性增生中发生的PTC发病率不断上升。针对这些生长因子和受体的靶向治疗用于分化型和未分化型甲状腺癌的管理。本研究旨在确定VEGF和VEGF受体(VEGFR)在甲状腺结节性增生和PTC中的表达。方法:一项横断面研究,基于2003年至2014年甲状腺切除标本中的113例结节性增生和67例PTC的石蜡包埋存档组织块。然后通过免疫组织化学对组织切片进行VEGF、VEGFR-1和VEGFR-2染色。还确定了淋巴结受累情况和甲状腺外扩展情况。结果:PTC患者的平均年龄为44.7±15.8岁,结节性增生患者为42.2±13.6岁。结节性增生和PTC之间VEGFR-1(p=0.028)和VEGFR-2(p=0.003)表达存在统计学差异。然而,两种疾病之间VEGF表达无显著差异(p=0.576)。VEGF和VEGFR-1的共表达在结节性增生(p=0.016)和PTC(p=0.03)中均显著,同时VEGF和VEGFR-2表达无相关关系(p>0.05)。淋巴结状态和甲状腺外扩展与年龄组、性别、VEGF和VEGFR表达之间无显著关联(p>0.05)。结论:VEGF、VEGFR-1和VEGFR-2在结节性增生和PTC中均呈过表达。VEGFR-1和VEGFR-2的表达在PTC中更显著,且VEGF和VEGFR-1存在相关共表达。因此,抑制VEGFR为甲状腺癌的肿瘤管理提供了一个有前景的方向。