Immunohistochemical analysis of vascular density and area in colorectal carcinoma using different markers and comparison with clinicopathologic prognostic factors
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Analysis of blood and lymphatic vessel in colorectal cancer is controversial in the literature, possibly due to variations in the methods of analysis. In this study, it was aimed to search for a reliable approach in the quantification of angio- and lymphangiovascular density and area as a prognostic factor and to compare such vessel counts in normal mucosa, adenomas and cancer. A retrospective study was performed on 60 sporadic colorectal cancer, 30 colorectal adenomas, and 10 colorectal non-neoplastic lesions. Archival tissues were submitted to immunohistochemical evaluation using antibodies to CD31, CD34, CD105, VEGF-A, VEGF-C, and D2-40. Microvessel density and total vascular area were determined by computer image analysis and values were compared in the three groups of lesions; the prognostic value of these parameters was evaluated in the group of colorectal cancer. Most markers showed progressive vessel counts from non-neoplastic tissue to carcinoma, both for microvessel density and total vascular area. Only microvessel density determined by CD34 in the central areas of the cancer correlated with recurrence/metastasis (p = 0.04) and survival (p = 0.02). Different methods of quantification (microvessel counting versus estimation of total vascular area), immunohistochemical markers (pan-endothelial marker versus neovessels and lymphatic markers), and areas of analysis (periphery versus inner portions of the lesion) were assessed using image analysis. The results corroborate the increase in vascularization of carcinoma and suggest that microvessel density determined by immunostaining for CD34 in the inner portion of the tumor might represent a prognostically relevant parameter in colorectal cancer.
- Benson AB. Epidemiology, disease progression, and economic burden of colorectal cancer. J Manag Care Pharm. 2007;13:5–18. Review.
- Buyse M, Piedbois P. Should Dukes’ B patients receive adjuvant therapy? A statistical perspective. Semin Oncol. 2001;28:20–4. CrossRef
- Byrne AM, Bouchier-Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med. 2005;9:777–94. Review. CrossRef
- Ono T, Miki C. Factors influencing tissue concentration of vascular endothelial growth factor in colorectal carcinoma. Am J Gastroenterol. 2000;95:1062–7. CrossRef
- Galizia G, Ferraracio F, Lieto E, et al. Prognostic value of p27, p53, and vascular endothelial growth factor in Dukes A and B colon cancer patients undergoing potentially curative surgery. Dis Colon Rectum. 2004;47:1904–14. CrossRef
- Kojima M, Shiokawa A, Nobuyuki O, et al. Clinical significance of nuclear morphometry at the invasive front of T1 colorectal cancer and relation to expression of VEGFA and VEGFC. Oncology. 2005;68:230–8. CrossRef
- Zheng S, Han MY, Xiao ZX, Peng JP, Dong Q. Clinical significance of vascular endothelial growth factor expression and neovascularization in colorectal carcinoma. World J Gastroenterol. 2003;9:1227–30.
- Rmali KA, Puntis CA, Jiang WG. Tumor associated angiogenesis in human colorectal cancer. Colorectal Dis. 2006;9:3–14. CrossRef
- Duff SE, Jeziorska M, Kumar S, Haboubi N, et al. Lymphatic vessel density, microvessel density and lymphangiogenic growth factor expression in colorectal cancer. Colorectal Dis. 2007;9:793–800. CrossRef
- Hu WG, Li JW, Feng B, et al. Vascular endothelial growth factors C and D represent novel prognostic markers in colorectal carcinoma using quantitative image analysis. Eur Surg Res. 2007;39:229–38. CrossRef
- Kaio E, Tanaka S, Kitadai Y, et al. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology. 2003;64:61–73. CrossRef
- Cao Y. Why and how do tumors stimulate lymphangiogenesis? Lymphat Res Biol. 2008;6:145–8. Review. CrossRef
- Gao Y, Zhong WX, Mu DB, et al. Distributions of angiogenesis and lymphangiogenesis in gastrointestinal intramucosal tumors. Ann Surg Oncol. 2008;15:1117–23. CrossRef
- Vermeulen PB, Van den Eynden GG, Huget P, et al. Prospective study of intramural microvessel density, p53 expression and survival in colorectal cancer. Br J Cancer. 1999;79:316–22. CrossRef
- Pavlopoulos PM, Konstantinidou AE, Agapitos E, et al. A morphometric study of neovascularization in colorectal carcinoma. Cancer. 1998;83:2067–75. CrossRef
- Prall F, Gringmuth U, Nizze H, Barten M. Microvessel densities and microvascular architecture in colorectal carcinomas and their liver metastases: significant correlation of high microvessel densities with better survival. Histopathology. 2003;42:482–91. CrossRef
- Akagi K, Ikeda Y, Sumiyoshi Y, Kimura Y, et al. Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development. Surgery. 2002;131:109–13. CrossRef
- Li C, Gardy R, Seon BK, et al. Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer. 2003;88:1424–31. CrossRef
- Clasper S, Royston D, Baban D, et al. A novel gene expression profile in lymphatics associated with tumor growth and nodal metastasis. Cancer Res. 2008;68:7293–303. CrossRef
- Romani AA, Borghetti AF, Del Rio P, et al. The risk of developing metastatic disease in colorectal cancer is related to CD105-positive vessel count. J Surg Oncol. 2006;93:446–55. CrossRef
- Barresi V, Vitarelli E, Tuccari G, Barresi G. Correlative study of microvessel density and 5-lipoxygenase expression in human sporadic colorectal cancer. Arch Pathol Lab Med. 2008;132:1807–12.
- Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15:434–40. CrossRef
- Longatto-Filho A, Pinheiro C, Ferreira L, et al. Peritumoural, but not intratumoural, lymphatic vessel density and invasion correlate with colorectal carcinoma poor-outcome markers. Virchows Arch. 2008;452:133–8. CrossRef
- Yan G, Zhou XY, Cai SJ, Zhang GH, et al. Lymphangiogenic and angiogenic microvessel density in human primary sporadic colorectal carcinoma. World J Gastroenterol. 2008;14:101–7. CrossRef
- Matsumoto K, Nakayama Y, Inoue Y, et al. Lymphatic microvessel density is an independent prognostic factor in colorectal cancer. Dis Colon Rectum. 2007;50:308–14. CrossRef
- Fogt F, Zimmerman RL, Ross HM, et al. Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40. Oncol Rep. 2004;11:47–50.
- International Union against Cancer /TNM Classification of Malignant Tumours (2009) 7th edition. Geneva, Switzerland. Available: http://www.uicc.org [accessed May 10, 2010].
- Giatromanolaki A, Sivridis E, Koukourakis MI. Angiogenesis in colorectal cancer: prognostic and therapeutic implications. Am J Clin Oncol. 2006;29:408–17. CrossRef
- Gao J, Knutsen A, Arbman G, et al. Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer. Dig Liver Dis. 2009;41:116–22. CrossRef
- Vermeulen PB, Gasparini G, Fox SB, et al. Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer. 2002;38:1564–79. Review. CrossRef
- Svagzdys S, Lesauskaite V, Pavalkis D, et al. Microvessel density as new prognostic cancer.marker after radiotherapy in rectal cancer. BMC Cancer. 2009;26:9–95.
- Ma YL, Peng JY, Zhang P, Liu WJ, et al. Immunohistochemical analysis revealed CD34 and Ki67 protein expression as significant prognostic factors in colorectal cancer. Med Oncol. 2010;27(2):304–9. CrossRef
- Nanashima A, Shibata K, Nakayama T, Tobinaga S, et al. Clinical significance of microvessel count in patients with metastatic liver cancer originating from colorectal carcinoma. Ann Surg Oncol. 2009;16(8):2130–7. CrossRef
- Yao X, Qian CN, Zhang ZF, et al. Two distinct types of blood vessels in clear cell renal cell carcinoma have contrasting prognostic implications. Clin Cancer Res. 2007;13:161–9. CrossRef
- Papadopoulos I, Giatromanolaki A, Koukourakis MI, Sivridis E. Tumour angiogenic activity and vascular survival ability in bladder carcinoma. J Clin Pathol. 2004;57:250–25. CrossRef
- Giatromanolaki A, Koukourakis MI, Sivridis E, et al. Invading edge vs. inner’ (edvin) patterns of vascularization: an interplay between angiogenic and vascular survival factors defines the clinical behaviour of non-small cell lung cancer. J Pathol. 2000;192:140–9. CrossRef
- Giatromanolaki A, Sivridis E, Simopoulos C, et al. Differential assessment of angiogenic activity and of vascular survival ability (VSA) in breast cancer. Clin Exp Metastasis. 2002;19:673–9. CrossRef
- Reinmuth N, Parikh AA, Ahmad SA, et al. Biology of angiogenesis in tumors of the gastrointestinal tract. Microsc Res Tech. 2003;60:199–207. Review. CrossRef
- Immunohistochemical analysis of vascular density and area in colorectal carcinoma using different markers and comparison with clinicopathologic prognostic factors
Volume 32, Issue 3 , pp 527-534
- Cover Date
- Print ISSN
- Online ISSN
- Springer Netherlands
- Additional Links
- Vascular density
- Vascular area
- Colorectal carcinoma
- Author Affiliations
- 1. Department of Pathology, Faculty of Medical Sciences, Laboratory of Investigative and Molecular Pathology, CIPED, FCM-Unicamp, Rua Tessália Viera de Camargo, 126, 13083-887, Campinas, São Paulo, Brazil