Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Prognostic Value of Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) Expression in Resected Non-small Cell Lung Cancer

수술로 절제된 비소세포폐암 조직에서 예후인자로서 VEGF와 bFGF 발현의 의의

  • Kim, Seung Joon (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Lee, Jung Mi (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Jin Sook (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kang, Ji Young (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Lee, Sang Hak (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Seok Chan (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Lee, Sook Young (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Chi Hong (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Ahn, Joong Hyun (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kwon, Soon Seog (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Young Kyoon (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Kwan Hyoung (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Moon, Hwa Sik (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Song, Jeong Sup (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Park, Sung Hak (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Moon, Seok Hwan (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine) ;
  • Wang, Yeong Pil (Department of Thoracic and Cardiovascular Surgery, The Catholic University of Korea College of Medicine)
  • 김승준 (가톨릭대학교 의과대학 내과학교실) ;
  • 이정미 (가톨릭대학교 의과대학 내과학교실) ;
  • 김진숙 (가톨릭대학교 의과대학 내과학교실) ;
  • 강지영 (가톨릭대학교 의과대학 내과학교실) ;
  • 이상학 (가톨릭대학교 의과대학 내과학교실) ;
  • 김석찬 (가톨릭대학교 의과대학 내과학교실) ;
  • 이숙영 (가톨릭대학교 의과대학 내과학교실) ;
  • 김치홍 (가톨릭대학교 의과대학 내과학교실) ;
  • 안중현 (가톨릭대학교 의과대학 내과학교실) ;
  • 권순석 (가톨릭대학교 의과대학 내과학교실) ;
  • 김영균 (가톨릭대학교 의과대학 내과학교실) ;
  • 김관형 (가톨릭대학교 의과대학 내과학교실) ;
  • 문화식 (가톨릭대학교 의과대학 내과학교실) ;
  • 송정섭 (가톨릭대학교 의과대학 내과학교실) ;
  • 박성학 (가톨릭대학교 의과대학 내과학교실) ;
  • 문석환 (가톨릭대학교 의과대학 흉부외과학교실) ;
  • 왕영필 (가톨릭대학교 의과대학 흉부외과학교실)
  • Received : 2007.11.15
  • Accepted : 2008.02.04
  • Published : 2008.03.30
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Abstract

Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

연구배경: 혈관신생은 종양의 성장과 유지 및 전이에 필수적이며 따라서 종양조직은 혈관신생을 위해 많은 종류의 혈관형성 촉진인자들을 생성하고 있다. VEGF와 bFGF는 혈관신생과 관련되는 물질로 본 연구에서는 폐암환자에서 조직 내 VEGF와 bFGF의 발현에 대해 알아보고자 하였다. 방법: 조직학적으로 샘암종 또는 편평상피세포암종으로 진단받고 완치의 목적으로 수술을 시행 받은 35명의 폐암환자 조직에서 VEGF 및 bFGF의 농도를 ELISA 방법으로 측정하였으며 이에 대한 임상적 양상을 후향적으로 분석하였다. 결과: VEGF 및 bFGF의 농도는 종양조직이 대조조직보다 유의하게 높았으며 T2+T3의 종양조직이 T1의 종양 조직보다 유의하게 VEGF의 농도가 높았다. 림프절 전이가 있었던 경우가 없었던 경우보다 종양조직에서 VEGF의 농도가 증가한 경향을 보였다(p=0.06). 하지만 VEGF 및 bFGF의 농도는 환자의 병기 및 생존율에 통계적으로 유의한 차이를 보이지 않았다. 결론: VEGF 및 bFGF 모두 종양조직에서 증가하였으나 VEGF만이 종양크기, 림프절 전이 등의 임상양상과 연관성을 보여주었다. 하지만 각각의 VEGF 및 bFGF의 종양조직 내 농도는 예후와 관련되지는 않았다.

Keywords

References

  1. Choi Y, Kim Y, Hong YC, Park SK, Yoo KY. Temporal changes of lung cancer mortality in Korea. J Korean Med Sci 2007;22:524-8 https://doi.org/10.3346/jkms.2007.22.3.524
  2. Ravdin PM, Davis G. Prognosis of patients with resected non-small cell lung cancer: impact of clinical and pathologic variables. Lung Cancer 2006;52:207-12 https://doi.org/10.1016/j.lungcan.2006.01.016
  3. Bremnes RM, Camps C, Sirera R. Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 2006;51:143-58 https://doi.org/10.1016/j.lungcan.2005.09.005
  4. Onn A, Herbst RS. Angiogenesis and lung cancer: implications for prognosis and treatment. Lancet Oncol 2007;8:460-1 https://doi.org/10.1016/S1470-2045(07)70153-5
  5. Anderson IC, Mari SE, Broderick RJ, Mari BP, Shipp MA. The angiogenic factor interleukin 8 is induced in non-small cell lung cancer/pulmonary fibroblast cocultures. Cancer Res 2000;60:269-72
  6. Iwasaki A, Kuwahara M, Yoshinaga Y, Shirakusa T. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC. Eur J Cardiothorac Surg 2004;25:443-8 https://doi.org/10.1016/j.ejcts.2003.11.031
  7. Papetti M, Herman IM. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 2002;282:C947-70 https://doi.org/10.1152/ajpcell.00389.2001
  8. Ferrara N. The role of VEGF in the regulation of physiological and pathological angiogenesis. EXS 2005;94:209-31
  9. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182-6 https://doi.org/10.1056/NEJM197111182852108
  10. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246:1306-9 https://doi.org/10.1126/science.2479986
  11. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005;69 Suppl 3:4-10 https://doi.org/10.1159/000088478
  12. Cebe-Suarez S, Zehnder-Fjallman A, Ballmer-Hofer K. The role of VEGF receptors in angiogenesis: complex partnerships. Cell Mol Life Sci 2006;63:601-15 https://doi.org/10.1007/s00018-005-5426-3
  13. Kiselyov A, Balakin KV, Tkachenko SE. VEGF/VEGFR signalling as a target for inhibiting angiogenesis. Expert Opin Investig Drugs 2007;16:83-107 https://doi.org/10.1517/13543784.16.1.83
  14. Szebenyi G, Fallon JF. Fibroblast growth factors as multifunctional signaling factors. Int Rev Cytol 1999;185:45-106
  15. Klagsbrun M. Mediators of angiogenesis: the biological significance of basic fibroblast growth factor (bFGF)-heparin and heparan sulfate interactions. Semin Cancer Biol 1992;3:81-7
  16. Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 2001;22:201-7 https://doi.org/10.1016/S0165-6147(00)01676-X
  17. Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, et al. Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 anti-body and anti-CD105 antibody. Clin Cancer Res 2001;7:3410-5
  18. Lee SN. The prognostic role of vascular endothelial growth factor (VEGF) expression and angiogenesis in curatively resected non-small cell lung cancer. J Korean Cancer Assoc 1999;31:1210-8
  19. Ko HJ, Park JH, Shim H, Yang SH, Jeong ET. Prognostic value of vascular endothelial growth factor (VEGF) in resected non-small cell lung cancer. Tuberc Respir Dis 2001;50:676-85 https://doi.org/10.4046/trd.2001.50.6.676
  20. Hemmerlein B, Kugler A, Ozisik R, Ringert RH, Radzun HJ, Thelen P. Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas. Virchows Arch 2001;439:645-52 https://doi.org/10.1007/s004280100464
  21. Rong Y, Durden DL, Van Meir EG, Brat DJ. 'Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis. J Neuropathol Exp Neurol 2006;65:529-39 https://doi.org/10.1097/00005072-200606000-00001