Immunohistochemical expression of VEGF in hepatocellular carcinoma and surrounding liver tissue

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Article Title:	Immunohistochemical expression of VEGF in hepatocellular carcinoma and surrounding liver tissue
Authors:	Norina Basa 1, Marioara Cornianu 2, Elena Lazăr 2, Alis Dema 2, Sorina Tăban 2, Daniela Lazăr 3, Codruţa Lăzureanu 2, Alexandra Faur 2, A. Tudor 4, Liana Moş 5, George Ciprian Pribac 5
Affiliation:	1County Hospital; 2Department of Pathology; 3Gastroenterology Clinic; 4Biophysics Department, University of Medicine and Pharmacy “Victor Babeş” Timişoara 5”Vasile Goldiş” Western University of Arad
Abstract:	Introduction: Angiogenesis is a fundamental process involved in malignant transformation and progression of cancer, in tumor growth and metastasis. VEGF plays an essential role in the angiogenesis of hepatocellular carcinoma (HCC). Method: We evaluated VEGF expression in 16 resected HCCs and in the surrounding liver tissue using the IHC staining method and monoclonal antibody anti-VEGF, clone VG1. The results were statistically analyzed using the Epi Info 6.04 program; we considered as significant the value < 0.05. Results: Positive VEGF expression was observed in 14 (87.7%) of the 16 patients with HCC and in 62.5% of the surrounding liver tissue (cirrhotic or non-cirrhotic), without significant differences between HCC and non-Tumor liver (0.11). Capsular infiltration (p=0.242), vascular invasion (p=0.383) and intrahepatic metastases (p=0.13) were observed more frequently in patients with positive VEGF expression. Conclusions: VEGF expression was higher in HCC than in cirrhotic nodules; our results suggest that VEGF can play an important role in the angiogenesis and prognosis of HCC, as well as in the angiogenesis of liver cirrhosis.
Keywords:	angiogenesis, VEGF, HCC, surrounding liver tissue
References:	An FQ, Matsuda M, Fujii H, Matsumoto Y. Expression of vascular endothelial growth factor in surgical specimens of hepatocellular carcinoma. J Cancer Res Clin Oncol 2000; 126: 153–160 Cejudo-Martin P, Morales-Ruiz M, Ros J, Navasa M, Fernandez-Varo G, Fuster J, Rivera F, Arroyo V, Rodes J, Jimenez W. Hypoxia is an inducer of vasodilator agents in peritoneal macrophages of cirrhotic patients. Hepatology 2002; 36: 1172–1179 Deli G, Jin C-H, Mu R, Yang S, Liang Y, Chen D, Makuuchi M. Immunohistochemical assessment of angiogenesis in hepatocellular carcinoma and surrounding cirrhotic liver tissues. World J Gastroenterol 2005; 11(7): 960-963. Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. Am J Pathol 1995; 146: 1029-1039. 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. Hepatology 1998; 27: 1554-1562. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Nat Cancer Inst 1990; 82: 4-6. Feng DY, Shen M, Zheng H, Cheng RX. Relationship between vascular endothelial growth factor expression and microvessel density in hepatocellular carcinomas and their surrounding liver tissue. Hunan Yike Daxue Xuebao 2000; 25: 132–134 Gullino PM, Ziche M, Alessandri G. Gangliosides, copper ions and angiogenic capacity of adult tissues. Cancer Metastasis Rev 1990; 9: 239-251. Helaly GF, Abou Shamaa LA. Influence of hepatitis C virus infection on circulating levels of sICAM-1 and VEGF in patients with hepatitis C and hepatocellular carcinoma (HCC) and their role in enhancing detection of HCC. Egypt J Immunol 2006; 13: 27-38. Hisai H, Kato J, Kobune M, et al. Increased expression of angiogenin in hepatocellular carcinoma in correlation with tumor vascularity. Clin Cancer Res 2003; 9: 4852-4859. Jeng KS, Sheen IS, Wang YC, et al. Prognostic significance of preoperative circulating vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma: A prospective study. World J Gastroenterol 2004;10: 643-648. Jinno K, Tanimizu M, Hyodo I, et al. Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker for metastasis in human hepatocellular carcinoma. J Gastroenterol 1998; 33: 376-382. Kim KR, Moon HE, Kim KW. Hypoxia-induced angiogenesis in human hepatocellular carcinoma. J Mol Med 2002; 80: 703–714 Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. Inhibition of vascular endothelial growth factor induced angiogenesis suppresses tumour growth in vivo. Nature 1993; 362: 841–844. Lang KJ, Kappel A, Goodall GJ. Hypoxia-inducible factor-1α mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia. Mol Biol Cell 2002; 13: 1792–1801 Li XM, Tang ZY, Zhou G, et al. Significance of vascular endothelial growth factor mRNA expression in invasion and metastasis of hepatocellular carcinoma. J Exp Clin Cancer Res 1998; 17: 13-17. Mandriota SJ, Pepper MS. Vascular endothelial growth factor- induced in vitro angiogenesis and plasminogen activator expression are dependent on endogenous basic fibroblast growth factor. J Cell Sci 1997; 110(Pt 18): 2293–2302 Mise M, Arii S, Higashituji H, Furutani M, Niwano M, Harada T, Ishigami S, Toda Y, Nakayama H, Fukumoto M, Fujita J, Imamura M. Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology 1996; 23: 455–464 Miura H, Kuroda M, et al. Increased expression of vascular endothelial growth factor in human hepatocellular carcinoma. J Hepatol 1997; 27: 854-861. Ohkubo K, Kato Y, Ichikawa T, et al. Viral load is a significant prognostic factor for hepatitis B virus associated hepatocellular carcinoma. Cancer 2002;94: 2663-2668. Pang R, Poon RT. Angiogenesis and antiangiogenic therapyin hepatocellular carcinoma. Cancer Lett 2006; 242:151-167. Park YN, Kim YB, Yang KM, Park C. Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis. Arch Pathol Lab Med 2000; 124: 1061–1065 Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumor angiogenesis factor in human gliomas in vivo. Nature 1992; 359: 845–848 Poon RT-P, Lau CP-Y, Cheung S-T, Yu W-C, Fan S-T. Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma. Cancer Res 2003; 63: 3121–3126. Shimamura T, Saito S, Morita K, et al. Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens. J Gastroenterol Hepatol 2000;15: 640-646. Shimoda K, Mori M, Shibuta K, Banner BF, Barnard GF. Vascular endothelial growth factor/vascular permeability factor mRNA expression in patients with chronic hepatitis C and hepatocellular carcinoma. Int J Oncol 1999; 14: 353–359 Steinbrech DS, Longaker MT, Mehrara BJ, Saadeh PB, Chin GS, Gerrets RP, Chau DC, Rowe NM, Gittes GK. Fibroblast response to hypoxia: The relationship between angiogenesis and matrix regulation. J Surg Res 1999; 84: 127–133 Suzuki K, nayashi N, Miyamoto Y, Yamamoto M, Ohkawa K, Ito Y, Sasaki Y, Yamaguchi Y, Nakase H, Noda K, Enomoto N, Ara K, Yamada Y, Yoshihara H, Tujimura T, Kawano K, Yoshihara Y, Kamada T. Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res 1996; 56: 3004-3009. Tseng P, Tai M, Huang C, Wang C, Lin J, Hung C, Chen C, Wang J, Lu S, Lee C, Changchien C, Hu T. Overexpression of VEGF is associated with positive p53 immunostaining in hepatocellular carcinoma (HCC) and adverse outcome of HCC patients. J Surg Oncol 2008; 98: 349-357. Yamaguchi R, Yano H, Nakashima O, et al. Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma. J Gastroenterol Hepatol 2006; 21: 152-160. Yamaguchi R, Yano H, Nakashima Y, et al. Expression and localization of vascular endothelial growth factor receptors in human hepatocellular carcinoma and non-HCC tissues. Oncol Rep 2000; 7: 725-729. Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology 1998; 28: 68- 77. Yao DF, Wu XH, Zhu Y, et al. Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2005; 4: 220-226. Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med 1998; 49: 407-424.
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