VEGF-C在肝癌組織的表達及意義_《中國普外基礎與臨床雜志》

作者：

葉義標 , 陳濤

中山大學孫逸仙紀念醫院(中山大學附屬第二醫院)肝膽外科(廣州 510120);

關鍵詞：

肝細胞肝癌血管內皮生長因子-C FMS樣酪氨酸激酶-4 CD34 免疫組織化學

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目的通過檢測血管內皮生長因子-C(VEGF-C)及其受體Flt-4在肝癌組織中的表達，分析它們與肝癌脈管形成及臨床病理特征之間的關系，以了解VEGF-C在肝癌進程中的作用。方法采用免疫組化染色法檢測62例肝細胞肝癌(HCC)組織及15例正常肝組織中VEGF-C和Flt-4的表達，并計算以CD34為標記的微血管密度(MVD)和以Flt-4為標記的淋巴管密度(LVD)，分析它們相互之間及各自與HCC臨床病理特征之間的關系。結果 HCC組織中VEGF-C及Flt-4的陽性表達率均明顯高于正常肝組織(P lt;0.05,P lt;0.01)。HCC組織中VEGF-C的表達與有無門靜脈癌栓、腫瘤組織學分化程度、術后復發及轉移有關(P lt;0.05,P lt;0.01)； Flt-4的表達與腫瘤組織學分化程度及術后復發有關(P lt;0.05,P lt;0.01)； MVD與腫瘤大小、TNM臨床分期、腫瘤組織學分化程度、有無門靜脈癌栓、術后復發和轉移有關(P lt;0.05,P lt;0.01)； LVD與腫瘤組織學分化程度、術后復發和轉移有關(P lt;0.05,P lt;0.01)。HCC組織中VEGF-C和Flt-4的表達及MVD和LVD這四者之間均兩兩呈正相關(P lt;0.01)。結論 VEGF-C和Flt-4在肝癌組織中高表達并與術后復發有關，且與MVD及LVD呈正相關，提示VEGF-C/Flt-4通路可能通過促進肝癌血管和淋巴管的生成從而影響肝癌的進展及預后。

引用本文： 葉義標,陳濤. VEGF-C在肝癌組織的表達及意義. 中國普外基礎與臨床雜志, 2010, 17(11): 1152-1157. doi: 復制

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8.	Yonemura Y, Endo Y, Fujita H, et al. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer [J]. Clin Cancer Res, 1999; 5(7): 1823-1829.
9.	Yonemura Y, Fushida S, Bando E, et al. Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3 in gastric cancer [J]. Eur J Cancer, 2001; 37(7): 918-923.
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13.	Liu XE, Sun XD, Wu JM. Expression and significance of VEGF-C and FLT-4 in gastric cancer [J]. World J Gastroenterol, 2004; 10(3): 352-355.
14.	Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas [J]. Int J Cancer, 2001; 93(5): 662-666.
15.	Noguchi T, Takeno S, Shibata T, et al. VEGF-C expression correlates with histological differentiation and metastasis in squamous cell carcinoma of the esophagus [J]. Oncol Rep, 2002; 9(5): 995-999.
16.	Auvinen MI, Sihvo EI, Ruohtula T, et al. Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma [J]. J Clin Oncol, 2002; 20(13): 2971-2979.
17.	Furudoi A, Tanaka S, Haruma K, et al. Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma [J]. Oncology, 2002; 62(2): 157-166.
18.	Akiyoshi F, Sata M, Suzuki H, et al. Serum vascular endothelial growth factor levels in various liver diseases [J]. Dig Dis Sci, 1998; 43(1): 41-45.
19.	El-Assal ON, Yamanoi A, Soda Y, et al. Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver [J]. Hepatology, 1998; 27(6): 1554-1562.
20.	崔曉楠, 候力. 組織微陣列方法檢測CD105、VEGF-C在肝癌組織中的表達 [J]. 醫學與哲學(臨床決策論壇版), 2006; 27(5): 39-41， 48.
21.	Takahashi Y, Bucana CD, Cleary KR, et al. p53, vessel count, and vascular endothelial growth factor expression in human colon cancer [J]. Int J Cancer, 1998; 79(1): 34-38.
22.	Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas [J]. Int J Cancer, 2001; 93(5): 662-666.
23.	Clarijs R, Ruiter DJ, de Waal RM. Lymphangiogenesis in malignant tumours: Does it occur? [J]. J Pathol, 2001; 193(2): 143-146.
24.	于大海, 溫玉明, 王昌美, 等. VEGFR-3表達與口腔癌淋巴道轉移的關系 [J]. 臨床口腔醫學雜志, 2001; 17(4): 243-245.
25.	蔣道榮, 姚登福, 祝勇, 等. 肝癌組織血管內皮因子表達及其臨床意義 [J]. 中國醫師雜志, 2004; 6(2): 158-160.
26.	Sugimachi K, Tanaka S, Taguchi K, et al. Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma [J]. J Clin Pathol, 2003; 56(11): 854-860.
27.	Padera TP, Kadambi A, di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics [J]. Science, 2002; 296(5574): 1883-1886.
28.	Stevenson DP, Milligan SR, Collins WP. Effects of platelet-derived endothelial cell growth factor/thymidine phosphorylase, substrate, and products in a three-dimensional model of angiogenesis [J]. Am J Pathol, 1998; 152(6): 1641-1646.

1. Jeng KS, Sheen IS, Wang YC, et al. Is the vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma of prognostic value after resection? [J]. World J Gastroenterol， 2004; 10(5): 676-681.
2. Kraft A, Weindel K, Ochs A, et al. Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease [J]. Cancer， 1999; 85(1): 178-187.
3. Yamaguchi R, Yano H, Nakashima O, et al. Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma [J]. J Gastroenterol Hepatol, 2006; 21(1 Pt 1): 152-160.
4. Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases [J]. EMBO J, 1996; 15(2): 290-298.
5. Hagedorn M, Bikfalvi A. Target molecules for anti-angiogenic therapy: from basic research to clinical trials [J]. Crit Rev Oncol Hematol, 2000; 34(2): 89-110.
6. Ogawa Y, Chung YS, Nakata B. Microvessel quantitation in invasive breast cancer by staining for factor Ⅷ-related antigen [J]. Br J Cancer, 1995; 71(6): 1297-1301.
7. 陳自強, 卞修武. 血管內皮生長因子家族 [J]. 國外醫學·生理、病理科學與臨床分冊， 2000; 20(3): 187-189.
8. Yonemura Y, Endo Y, Fujita H, et al. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer [J]. Clin Cancer Res, 1999; 5(7): 1823-1829.
9. Yonemura Y, Fushida S, Bando E, et al. Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3 in gastric cancer [J]. Eur J Cancer, 2001; 37(7): 918-923.
10. Ichikura T, Tomimatsu S, Ohkura E, et al. Prognostic significance of the expression of vascular endothelial growth factor (VEGF) and VEGF-C in gastric carcinoma [J]. J Surg Oncol, 2001; 78(2): 132-137.
11. Takahashi A, Kono K, Itakura J, et al. Correlation of vascular endothelial growth factor-C expression with tumor-infiltrating dendritic cells in gastric cancer [J]. Oncology, 2002; 62(2): 121-127.
12. Ishikawa M, Kitayama J, Kazama S, et al. Expression of vascular endothelial growth factor C and D (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma [J]. Jpn J Clin Oncol, 2003; 33(1): 21-27.
13. Liu XE, Sun XD, Wu JM. Expression and significance of VEGF-C and FLT-4 in gastric cancer [J]. World J Gastroenterol, 2004; 10(3): 352-355.
14. Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas [J]. Int J Cancer, 2001; 93(5): 662-666.
15. Noguchi T, Takeno S, Shibata T, et al. VEGF-C expression correlates with histological differentiation and metastasis in squamous cell carcinoma of the esophagus [J]. Oncol Rep, 2002; 9(5): 995-999.
16. Auvinen MI, Sihvo EI, Ruohtula T, et al. Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma [J]. J Clin Oncol, 2002; 20(13): 2971-2979.
17. Furudoi A, Tanaka S, Haruma K, et al. Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma [J]. Oncology, 2002; 62(2): 157-166.
18. Akiyoshi F, Sata M, Suzuki H, et al. Serum vascular endothelial growth factor levels in various liver diseases [J]. Dig Dis Sci, 1998; 43(1): 41-45.
19. El-Assal ON, Yamanoi A, Soda Y, et al. Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver [J]. Hepatology, 1998; 27(6): 1554-1562.
20. 崔曉楠, 候力. 組織微陣列方法檢測CD105、VEGF-C在肝癌組織中的表達 [J]. 醫學與哲學(臨床決策論壇版), 2006; 27(5): 39-41， 48.
21. Takahashi Y, Bucana CD, Cleary KR, et al. p53, vessel count, and vascular endothelial growth factor expression in human colon cancer [J]. Int J Cancer, 1998; 79(1): 34-38.
22. Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas [J]. Int J Cancer, 2001; 93(5): 662-666.
23. Clarijs R, Ruiter DJ, de Waal RM. Lymphangiogenesis in malignant tumours: Does it occur? [J]. J Pathol, 2001; 193(2): 143-146.
24. 于大海, 溫玉明, 王昌美, 等. VEGFR-3表達與口腔癌淋巴道轉移的關系 [J]. 臨床口腔醫學雜志, 2001; 17(4): 243-245.
25. 蔣道榮, 姚登福, 祝勇, 等. 肝癌組織血管內皮因子表達及其臨床意義 [J]. 中國醫師雜志, 2004; 6(2): 158-160.
26. Sugimachi K, Tanaka S, Taguchi K, et al. Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma [J]. J Clin Pathol, 2003; 56(11): 854-860.
27. Padera TP, Kadambi A, di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics [J]. Science, 2002; 296(5574): 1883-1886.
28. Stevenson DP, Milligan SR, Collins WP. Effects of platelet-derived endothelial cell growth factor/thymidine phosphorylase, substrate, and products in a three-dimensional model of angiogenesis [J]. Am J Pathol, 1998; 152(6): 1641-1646.

《中國普外基礎與臨床雜志》

VEGF-C在肝癌組織的表達及意義

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《中國普外基礎與臨床雜志》

VEGF-C在肝癌組織的表達及意義

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