Increased expression of vascular endothelial growth factor C in papillary thyroid carcinoma correlates with cervical lymph node metastases
Increased expression of vascular endothelial growth factor C in papillary thyroid carcinoma correlates with cervical lymph node metastases
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DOI：
10.1158/1078-0432.ccr-05-0646
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发表时间：
2005-11-15
影响因子：
11.5
通讯作者：
Luk, JM
中科院分区：
文献类型：
--
作者：
Yu, XM;Lo, CY;Luk, JM
目的：尽管近年来研究表明甲状腺乳头状癌（PTC）中血管内皮生长因子C（VEGF-C）mRNA表达上调，但VEGF-C在淋巴结转移中的作用仍不清楚，本研究旨在探讨VEGF-C免疫反应蛋白在PTC中的表达模式及其与颈部淋巴结转移的关系。 设计：组织样本取自 39 个 PTC 标本（20 个有淋巴结转移，19 个无淋巴结转移）以及 20 个良性甲状腺结节。通过使用特异性抗 VEGF-C 抗体在来自 PTC 的配对肿瘤和非肿瘤组织中进行免疫印迹来评估 VEGF-C 蛋白的过度表达。将数据与患者的临床病理特征和淋巴结转移进行比较。对选定的石蜡切片进行免疫组织化学染色，以确定 VEGF-C 的细胞定位并评估 PTC 病变中的 flt-4（或 VEGFR-3）阳性血管密度。结果：在 69% 的 PTC 和 5% 的良性甲状腺标本中检测到 VEGF-C 过度表达。当比较PTC的转移组和非转移组时，在肿瘤（P = 0.004）和邻近非肿瘤组织（P = 0.011）中检测到较高的VEGF-C表达水平。在PTC肿瘤组织和转移淋巴结中证实了VEGF-C免疫染色阳性，这与肿瘤和瘤周组织中flt-4阳性血管密度相关。 PTC中VEGF-C蛋白表达增加与淋巴结转移（P = 0.004）和淋巴管渗透（P = 0.001）相关，但与其他临床病理变量无关。结论：VEGF-C免疫反应蛋白在PTC病灶中过度表达，与淋巴结转移相关。VEGF-C表达可能在PTC病灶中发挥重要作用。 VEGF-C 在 PTC 淋巴管生成中的作用，需要进一步研究来评估 VEGF-C 作为肿瘤转移至颈部淋巴结的分子标志物的临床应用。
Purpose: Despite recent studies showing that vascular endothelial growth factor C (VEGF-C) mRNA is up-regulated in papillary thyroid carcinoma (PTC), the role of VEGF-C in lymph node metastasis is still unclear, The aim of this study is to investigate the expression pattern of VEGF-C immuncireactive protein in PTC and its relationship with cervical lymph node metastasis.Experimental Design: Tissue samples were obtained from 39 specimens of PTC (20 with and 19 without lymph node metastasis) as well as 20 benign thyroid nodules. Overexpression of the VEGF-C protein was evaluated by immunoblotting with specific anti-VEGF-C antibody in paired tumor and nontumor tissues from PTC. The data were compared with patients' clinicopathologic features and lymph node metastasis. lmmunohistochemical staining was done on selected paraffin sections to determine cellular localization ofVEGF-C and to assess flt-4 (orVEGFR-3) - positive vessel density in PTC lesions.Results: Overexpression of VEGF-C was detected in 69% of the PTC and in 5% of the benign thyroid specimens. When comparing between the metastatic and nonmetastatic groups of PTC, a higher expression level of VEGF-C was detected in both the tumor (P = 0.004) and adjacent nontumor tissues (P = 0.011). Positive immuncistaining forVEGF-C was confirmed in PTC tumor tissues and metastatic lymph nodes, which correlated with flt-4-positive vessel density in tumor and peritumor tissues. The increased expression of VEGF-C protein in PTC is associated with lymph node metastasis (P = 0.004) and lymphovascular permeation (P = 0.001) but is independent of other clinicopatholgic variables.Conclusions: TheVEGF-C immuncireactive protein is overexpressed in PTC lesions, which correlates with lymph node metastases.VEGF-C expression may play a role in lymph a ng iogenesis of PTC and further study is necessary to evaluate the clinical application of VEGF-C as a molecular marker for tumor metastases to cervical lymph nodes.