간 전이를 동반한 대장암에서의 VEGF-A, VEGFR-1, VEGFR-2 발현 양상과 미세혈관 밀도의 비교
Differences in Expression of VEGF-A, VEGFR-1, VEGFR-2 and Microvessel Density in Colorectal Cancer with Liver Metastasis
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Background : Colorectal cancer (CRC) is one of the most common malignant neoplasms and is a leading cause of mortality worldwide. Metastasis to the liver is a frequent event in patients with CRC. An essential step in the metastatic cascade is angiogenesis. Methods : This study included 45 patients who underwent a partial colectomy with hepatic resection for CRC with hepatic metastases. Immunohistochemistry was performed using vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)-1, VEGFR-2, and CD34 antibodies to examine the relationship between CRC with liver metastases and angiogenesis. Results : CRC showed significantly stronger expression of VEGF-A, VEGFR-1, and VEGFR-2 than liver metastases (p < 0.05). Microvessel density was also higher in CRC than in liver metastases (p < 0.05). Conclusions : Compared with previous studies, we found a higher expression of VEGF-A, VEGFR-1, VEGFR-2, and microvessel density in CRC than in liver metastases, which could be ascribed to a difference in vessel distribution and blood supply in each organ. Given its profuse blood supply and distinct cell populations, the liver might provide a rich milieu for tumor cell growth with less expression of angiogenesis-inducing agents.
Abstract
Background : Colorectal cancer (CRC) is one of the most common malignant neoplasms and is a leading cause of mortality worldwide. Metastasis to the liver is a frequent event in patients with CRC. An essential step in the metastatic cascade is angiogenesis. Methods : This study included 45 patients who underwent a partial colectomy with hepatic resection for CRC with hepatic metastases. Immunohistochemistry was performed using vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)-1, VEGFR-2, and CD34 antibodies to examine the relationship between CRC with liver metastases and angiogenesis. Results : CRC showed significantly stronger expression of VEGF-A, VEGFR-1, and VEGFR-2 than liver metastases (p < 0.05). Microvessel density was also higher in CRC than in liver metastases (p < 0.05). Conclusions : Compared with previous studies, we found a higher expression of VEGF-A, VEGFR-1, VEGFR-2, and microvessel density in CRC than in liver metastases, which could be ascribed to a difference in vessel distribution and blood supply in each organ. Given its profuse blood supply and distinct cell populations, the liver might provide a rich milieu for tumor cell growth with less expression of angiogenesis-inducing agents.
참고문헌 (24)
- 신명희, "서울시 암 발생률의 10년간 추이: 1993-2002", 예방의학회지, 41(2), pp.92~99 (2008), 대한예방의학회
- Bird NC, "Biology of colorectal liver metastases:a review", J Surg Oncol, 94, pp.68~80 (2006)
- Parkin DM, "Global cancer statistics in the year 2000", Lancet Oncol, 2, pp.533~543 (2001)
- Liu YN, "Regulatory mechanisms controlling human E-cadherin gene expression", Oncogene, 24, pp.8277~8290 (2005)
- Folkman J, "What is the evidence that tumors are angiogenesis dependent?", J Natl Cancer Inst, 82, pp.4~6 (1990)
- Hanahan D, "Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis", Cell, 86, pp.353~364 (1996)
- Ferrara N, "The biology of VEGF and its receptors", Nat Med, 9, pp.669~676 (2003)
- George M, "VEGF-A,VEGF-C,and VEGF-D in colorectal cancer progression", Neoplasia, 3, pp.420~427 (2001)
- Roskoski R Jr, "Vascular endothelial growth factor(VEGF)signaling in tumor progression", Crit Rev Oncol Hematol, 62, pp.179~213 (2007)
- Ono T, "Factors influencing tissue concentration of vascular endothelial growth factor in colorectal carcinoma", Am J Gastroenterol, 95, pp.1062~1067 (2000)
- Wong MP, "Vascular endothelial growth factor is up-regulated in the early pre-malignant stage of colorectal tumour progression", Int J Cancer, 81, pp.845~850 (1999)
- Greene FL, "AJCC cancer staging manual. 6th ed" (2002), Springer-Verlag
- 이경화, "골거대세포종에서 혈관신생과 VEGF 및 MMP-9의 발현과 임상양상의 상관성에 관한 연구", The Korean Journal of Pathology, 40(6), pp.420~426 (2006), 대한병리학회
- Bosari S, "Microvessel quantitation and prognosis in invasive breast carcinoma", Hum Pathol, 23, pp.755~761 (1992)
- Takeda A, "Role of angiogenesis in the development and growth of liver metastasis", Ann Surg Oncol, 9, pp.610~616 (2002)
- Terayama N, "An immunohistochemical study of tumour vessels in metastatic liver cancers and the surrounding liver tissue", Histopathology, 29, pp.37~43 (1996)
- Terayama N, "Histologic growth patterns of metastatic carcinomas of the liver", Jpn J Clin Oncol, 26, pp.24~29 (1996)
- Cascinu S, "Differences of vascular endothelial growth factor(VEGF)expression between liver and abdominal metastases from colon cancer:implications for the treatment with VEGF inhibitors", Clin Exp Metastasis, 18, pp.651~655 (2000)
- 전광식, "직장 결장암의 간전이 환자에서 VEGF-A, C, D 발현의 비교연구", 대한외과학회지, 76(5), pp.307~315 (2009), 대한외과학회
- Duff SE, "Vascular endothelial growth factors and receptors in colorectal cancer:implications for anti-angiogenic therapy", Eur J Cancer, 42, pp.112~117 (2006)
- Dirix LY, "Serum basic fibroblast growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer", Ann Oncol, 7, pp.843~848 (1996)
- Beckner ME, "Factors promoting tumor angiogenesis", Cancer Invest, 17, pp.594~623 (1999)
- Dachs GU, "Microenvironmental control of gene expression:implications for tumor angiogenesis,progression,and metastasis", Semin Radiat Oncol, 8, pp.208~216 (1998)
- Fukumura D, "Effect of host microenvironment on the microcirculation of human colon adenocarcinoma", Am J Pathol, 151, pp.679~688 (1997)