Yu Xiao-Min, Lo Chung-Yau, Chan Wai-Fan, Lam King-Yin, Leung Pauline, Luk John M
Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
Clin Cancer Res. 2005 Nov 15;11(22):8063-9. doi: 10.1158/1078-0432.CCR-05-0646.
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 immunoreactive protein in PTC and its relationship with cervical lymph node metastasis.
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. Immunohistochemical staining was done on selected paraffin sections to determine cellular localization of VEGF-C and to assess flt-4 (or VEGFR-3)-positive vessel density in PTC lesions.
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 immunostaining for VEGF-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.
The VEGF-C immunoreactive protein is overexpressed in PTC lesions, which correlates with lymph node metastases. VEGF-C expression may play a role in lymphangiogenesis 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.
尽管近期研究表明血管内皮生长因子C（VEGF-C）mRNA在甲状腺乳头状癌（PTC）中上调，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。
从39例PTC标本（20例有淋巴结转移，19例无淋巴结转移）以及20例甲状腺良性结节中获取组织样本。通过用特异性抗VEGF-C抗体对PTC配对的肿瘤组织和非肿瘤组织进行免疫印迹，评估VEGF-C蛋白的过表达情况。将数据与患者的临床病理特征及淋巴结转移情况进行比较。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flt-4（或VEGFR-3）阳性血管密度。
在69%的PTC中检测到VEGF-C过表达，而在5%的甲状腺良性标本中检测到。在PTC的转移组和非转移组之间进行比较时，在肿瘤组织（P = 0.004）和相邻非肿瘤组织（P = 0.011）中均检测到较高水平的VEGF-C表达。在PTC肿瘤组织和转移淋巴结中证实了VEGF-C的阳性免疫染色，这与肿瘤组织和肿瘤周围组织中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）和淋巴管浸润（P = 0.001）相关，但与其他临床病理变量无关。
VEGF-C免疫反应蛋白在PTC病变中过表达，这与淋巴结转移相关。VEGF-C表达可能在PTC的淋巴管生成中起作用，有必要进一步研究以评估VEGF-C作为颈部淋巴结肿瘤转移分子标志物的临床应用。
