VEGF受体3在乳腺癌组织中的表达及其意义_《中国修复重建外科杂志》

作者：

吴建忠 ¹ , 陈琳 ¹ , 周文斌 ¹ , 刘晓安 ¹ , 陈欣 ¹ , 苗登顺 ²

1 南京医科大学第一附属医院普通外科（南京，210029）;;
2 南京医科大学基础医学院;

关键词：

乳腺癌 VEGF受体3 淋巴结转移

DOI：

10.7507/1002-1892.20130327

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的探讨VEGF受体3（VEGF receptor 3，VEGFR-3）在乳腺癌组织中的表达，分析其表达与乳腺癌临床病理因素的关系，为乳腺癌的临床治疗及预后判断提供依据。方法取2004年3月－2007月6月接受乳腺癌切除术的173例女性患者乳腺癌组织存档石蜡标本（实验组），应用组织芯片技术构建乳腺癌组织芯片，HE染色判断组织芯片质量，免疫组织化学染色观察VEGFR-3表达情况；并以同期接受乳腺良性病变切除术的19例女性患者乳腺组织存档石蜡标本作为对照（对照组）。将实验组患者按照年龄、肿瘤直径、腋窝淋巴结转移情况、病理分期以及雌激素受体、孕激素受体和人EGF受体2（human EGF receptor 2，HER-2）基因表达情况分组，比较VEGFR-3阳性表达率。结果HE染色示两组组织芯片质量较好，能代表相应疾病组织病理学形态。免疫组织化学染色观察示，实验组中96例（55.5%）可见VEGFR-3表达阳性，对照组均未见阳性染色。不同年龄及雌激素受体、孕激素受体表达与否，VEGFR-3阳性表达率比较差异均无统计学意义（P gt; 0.05），肿瘤越大、病理分期越高，VEGFR-3阳性表达率显著提高（P lt; 0.05）；腋窝淋巴结转移者及HER-2基因表达阳性者VEGFR-3阳性表达率明显高于各自阴性表达者（P lt; 0.05）。结论VEGFR-3在乳腺癌组织中的表达与淋巴结转移关系密切，有望成为新的判断预后指标及治疗靶点。

引用本文： 吴建忠,陈琳,周文斌,刘晓安,陈欣,苗登顺. VEGF受体3在乳腺癌组织中的表达及其意义. 中国修复重建外科杂志, 2013, 27(12): 1487-1491. doi: 10.7507/1002-1892.20130327 复制

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16.	Valtola R, Salven P, Heikkilä P, et al. VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am J Pathol, 1999, 154(5): 1381-1390.
17.	Kojima H, Shijubo N, Yamada G, et al. Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma. Cancer, 2005, 104(8): 1668-1677.
18.	Mylona E, Alexandrou P, Mpakali A, et al. Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)- C and -D and VEGF receptor 3 in invasive breast carcinoma. Eur J Surg Oncol, 2007, 33(3): 294-300.
19.	Arinaga M, Noguchi T, Takeno S, et al. Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma. Cancer, 2003, 97(2): 457-464.
20.	Saintigny P, Kambouchner M, Ly M, et al. Vascular endothelial growth factor-C and its receptor VEGFR-3 in non-small-cell lung cancer: concurrent expression in cancer cells from primary tumorand metastatic lymph node. Lung Cancer, 2007, 58(2): 205-213.
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22.	Kodera Y, Katanasaka Y, Kitamura Y, et al. Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3. Breast Cancer Res, 2011, 13(3): R66.
23.	Matsui J, Funahashi Y, Uenaka T, et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res, 2008, 14(17): 5459-5465.

1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90.
2. Karkkainen MJ, Petrova TV. Vascular endothelial growth factor receptors in regulation of angiogenesis and lymphangiogenesis. Oncogene, 2000, 19(49): 5598-5605．.
3. Laakkonen P, Waltari M, Holopainen T, et al. Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth. Cancer Res, 2007, 67(2): 593-599.
4. Achen MG, Mann GB, Stacker SA. Targeting lymphangiogenesis to prevent tumour metastasis. Br J Cancer, 2006, 94(10): 1355-1360.
5. Petrova TV, Bono P, Holnthoner W, et al. VEGFR-3 expression is restricted to blood and lymphatic vessels in solid tumors. Cancer Cell, 2008, 13(6): 554-556.
6. Sauter G, Simon R, Hillan K. Tissue microarrays in drug discovery. Nat Rev Drug Discov, 2003, 2(12): 962-972.
7. Torhorst J, Bucher C, Kononen J, et al. Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol, 2001, 159(6): 2249-2256.
8. Nocito A, Bubendorf L, Tinner EM, et al. Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol, 2001, 194(3): 349-357.
9. Moch H, Schraml P, Bubendorf L, et al. High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. Am J Pathol, 1999, 154(4): 981-986.
10. Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med, 1998, 4(7): 844-847.
11. Hirakawa S, Brown LF, Kodama S, et al. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood, 2007, 109(3): 1010-1017.
12. Tobler NE, Detmar M. Tumor and lymph node lymphangiogenesis—impact on cancer metastasis. J Leukoc Biol, 2006, 80(4): 691-696.
13. Kriehuber E, Breiteneder-Geleff S, Groeger M, et al. Isolation and characterization of dermal lymphatic and blood endothelial cells reveal stable and functionally specialized cell lineages. J Exp Med, 2001, 194(6): 797-808.
14. Oliver G. Lymphatic vasculature development. Nat Rev Immunol, 2004, 4(1): 35-45.
15. White JD, Hewett PW, Kosuge D, et al. Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. Cancer Res, 2002, 62(6): 1669-1675.
16. Valtola R, Salven P, Heikkilä P, et al. VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am J Pathol, 1999, 154(5): 1381-1390.
17. Kojima H, Shijubo N, Yamada G, et al. Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma. Cancer, 2005, 104(8): 1668-1677.
18. Mylona E, Alexandrou P, Mpakali A, et al. Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)- C and -D and VEGF receptor 3 in invasive breast carcinoma. Eur J Surg Oncol, 2007, 33(3): 294-300.
19. Arinaga M, Noguchi T, Takeno S, et al. Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma. Cancer, 2003, 97(2): 457-464.
20. Saintigny P, Kambouchner M, Ly M, et al. Vascular endothelial growth factor-C and its receptor VEGFR-3 in non-small-cell lung cancer: concurrent expression in cancer cells from primary tumorand metastatic lymph node. Lung Cancer, 2007, 58(2): 205-213.
21. Kurenova EV, Hunt DL, He D, et al. Vascular endothelial growth factor receptor-3 promotes breast cancer cell proliferation, motility and survival in vitro and tumor formation in vivo. Cell Cycle, 2009, 8(14): 2266-2280.
22. Kodera Y, Katanasaka Y, Kitamura Y, et al. Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3. Breast Cancer Res, 2011, 13(3): R66.
23. Matsui J, Funahashi Y, Uenaka T, et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res, 2008, 14(17): 5459-5465.

《中国修复重建外科杂志》

VEGF受体3在乳腺癌组织中的表达及其意义

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《中国修复重建外科杂志》

VEGF受体3在乳腺癌组织中的表达及其意义

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