Abstract
It has previously been reported that intratumoral microvessel density (IMD), and the expression of bFGF and nm23-H1 are useful prognostic markers in colorectal cancer (CRC). In this study, a total of 100 CRCs were evaluated histopathologically, and IMD, bFGF and nm23-H1 expression were assessed by immunohistochemistry. IMD of patients increased with grade and stage, and this increase was statistically significant (p<0.05). A significantly higher incidence of high bFGF expression scores was also associated with increasing grade and stage (p<0.05). However, there was no significant difference between the grades in nm23-H1 expression (p=0.234). nm23-H1 expression occurred with lower incidence in stages C1, C2 and D than in stages B1 and B2 (p<0.05). Thus, a negative correlation was found between nm23-H1 expression and stage or lymph node metastasis (LNM) (p<0.05). IMD and bFGF expression were positively correlated with grade, stage, LNM, and lymphovascular invasion. Although positive correlation was found between IMD and bFGF, nm23-H1 expression negatively correlated with both of them. As a result, in clinical practice, increased IMD and bFGF expression and decreased nm23-H1 expression may provide valuable information in characterizing the malignant phenotype.
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References
Harpaz N, Saxena R: Large intestine. In: Modern Surgical Pathology. (Eds: Weidner N, Cote RJ, Suster S, Weis LM). 1st Edition, Saunders, Philadelphia, 2003, pp 749–852
Vermeulen PB, Van den Eynden GG, Huget P, et al: Prospective study of intratumoral microvessel density, p53 expression and survival in colorectal cancer. Br J Cancer 79:316–322, 1999
Weidner N, Semple JP, Welch WR, et al: Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma. N Eng J Med 324: 1–8, 1991
Graham CH, Rivers J, Kerbel RS, et al: Extent of vascularization as a prognostic indicator in thin (<0.76 mm) malignant melanomas. Am J Pathol 145: 510–514, 1994
Smith-McCune KK, Weidner N: Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res 54:800–804, 1994
Goi T, Fujioka M, Satoh Y, et al: Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine glands derived vascular endothelial growth factor, as a new angiogenic factor. Cancer Res 64: 1906–1910, 2004
Saad RS, Liu YL, Nathan G, et al: Endoglin (CD 105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 17: 197–203, 2004
Fenjvesi A: Prognostic significance of tumor-induced angiogenesis in colorectal carcinoma. Med Pregl 56: 263–268, 2003
Aotake T, Lu C, Chiba Y, et al: Changes of angiogenesis and tumor cell apoptosis during colorectal carcinogenesis. Clin Cancer Res 5: 135–142, 1999
Shan YS, Lee JC, Chow NH, et al: Immunohistochemical microvessel count is not a reliable prognostic predictor in colorectal carcinoma. Hepatogastroenterol 50: 1316–1320, 2003
Banner BF, Whitehause R, Baker SP, et al: Tumor angiogeuesis in stage II colorectal carcinoma. Association with survival. Am J Clin Pathol 109: 733–737, 1998
Bossi P, Viale G, Lee AKC, et al: Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations. Cancer Res 55: 5049–5053, 1995
Saito S, Tsuno N, Nagawa H, et al: Expression of platelet-derived endothelial cell growth factor correlates with good prognosis in patients with colorectal carcinoma. Cancer 88: 42–49, 2000
Leung DW, Cachianes G, Kuang WJ, et al: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246: 1306–1309, 1989
New B, Yeoman L: Identification of basic fibroblast growth factor sensitivity and receptor and ligand expression in human colon tumor cell lines. Cell Physiol 150: 320–326, 1992
Steeg PS, Bevilacqua G, Kopper L et al: Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80: 200–204, 1998
Tannapfel A, Kockerling F, Katalinic A, et al: Expression of nm23-Hl predicts lymph node involvement in colorectal carcinoma. Dis Colon Rectum 38: 651–654, 1995
Ayhan A, Yasui W, Yokozaki H, et al: Reduced expression of nm23-Hl protein is associated with advanced tumor stage and distant metastases in human colorectal carcinomas. Virchows Arch B Cell Pathol 63: 213–218, 1993
Heide I, Theide C, Poppe K, et al: Expression and mutational analysis of nm23-Hl in liver metastases of colorectal cancer. Br J Cancer 70: 1267–1271, 1994
Lee JC, Lin YJ, Chow NH, et al: Reappraisal of the role of nm23-Hl in colorectal cancers. J Surg Oncol 76: 58–62, 2001
Garinis G A, Manolis EN, Spanakis NE, et al: High frequency of concomitant nm23-Hl and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas. J Mol Med 81: 256–263, 2003
George ML, Dzik-Jurasz ASK, Padhani AR, et al: Non-invasive methods of assessing angiogenesis and their value in predicting response to treatment in colorectal cancer. Br J Surg 88: 1628–1636, 2001
Lackner C, Jukic Z, Tsybrovskyy O, et al.: Prognostic relevance of tumor-associated macrophages and von Willebrand factorpositive microvessels in colorectal cancer. Virchows Arch 445:160–167, 2004
Hawighorts H, Knapstein PG, Knapp M.V, et al: Uterine cervical carcinoma: Comparison of standard and pharmacokinetic analysis of time intensity curves for assessment of tumor angiogenesis and patient survival. Cancer Res 58: 3598–3602, 1998
Tomisaki S, Ohno S, Ichiyoshi Y, et al: Microvessel. quantification and its possible relation with liver metastasis in colorectal cancer. Cancer 77: 1722–1728, 1996
Tanigawa N, Amaya H, Matsumara M, et al: Tumor angiogenesis and mode of metastasis in patients with colorectal cancer. Cancer Res 57:1043–1046, 1997
Lindmark G, Gerdin B, Sundberg C, et al: Prognostic significance of the microvascular count in colorectal cancer. J Clin Oncol 14: 461–466, 1996
Takahashi Y, Kitadai Y, Bucana CD, et al: Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55: 3964–3968, 1995
Frank RE, Saclarides TJ, Leurgans S, et al: Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer. Ann Surg 222: 695–699, 1995
White JL, Hewett PL, Kosuge D, et al: Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. Cancer Res 62:1669–1675, 2002
Li Z-P, Meng Q-F, Sun C-H, et al: Tumor angiogenesis and dynamic CT in colorectal carcinoma: Radiologic-pathologic correlation. World J Gastroenterol 11: 1287–1291, 2005
Basilica C, Moscatelli D: The FGF family of growth factors and oncogenes. Adv Cancer Res 59: 115–125, 1992
Landriscina M, Cassano A, Ratio C et al: Quantitative analysis of basic fibroblast growth factor and vascular endothelial growth factor in human colorectal cancer. Br J Cancer 78: 765–770, 1998
Zheng S, Han MY, Xiao ZX, et al: Clinical significance of vascular endothelial growth factor expression and neovascularization in colorectal carcinoma. World J Gastroenterol 9: 1227–1230, 2003
Takahashi Y, Tucker SL, Kitadai Y, et al: Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. Arch Surg 132: 541–546, 1997
Stahl JA, Leone A, Rosengard AM, et al: Identification of a second human nm23-Hl gene, nm23-Hl-H2. Cancer Res 51: 445–449, 1991
Xerri L, Grob JJ, Battyani Z, et al.: nm23-Hl expression in metastasis of malignant melanoma is a predictive prognostic parameter correlated with survival. Br J Cancer 70: 1224–1228, 1994
Yamaguchi A, Urano T, Goi T, et al: Expression of human nm23-Hl and nm23-Hl-H2 proteins in hepatocelluiar carcinoma. Cancer 73: 2280–2284, 1994
Kodera Y, Isobe KI, Yamauchi M et al: Expression of nm23-Hl RNA levels in human gastric cancer tissues. Cancer 73: 259–265, 1994
Zou M, Shi Y, al-Sedairy S, et al: High levels of nm23-H1 gene expression in advanced stage of thyroid carcinomas. Br J Cancer 68: 385–388, 1993
Engel M, Theisinger B, Seib T, et al: High levels of nm23-H1 and nm23-H1-H2 messenger RNA in human squamous-cell lung carcinoma are associated with poor differentiation and advanced tumor stages. Int J Cancer 55: 375–379, 1993
Zeng ZS, Hsu S, Zhang ZF, et al: High level of nm23-Hl gene expression is associated with local colorectal cancer progression not with metastasis. Br J Cancer 70: 1025–1030, 1994
Yamaguchi A, Urana T, Fushida S, et al: Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis. Cancer 68: 1020–1024, 1993
Lindmark G: nm23-Hl immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer. Br J Cancer 74: 1413–1418, 1996
Sarris M, Lee CS: Nm23-Hl protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver. Eur J Surg Oncol 27: 170–174, 2001
Soliani P, Ziegler S, Romani A et al: Prognostic significance of nm23-H1 gene product expression in patients with colorectal carcinoma treated with radical intent. Oncol Rep 11: 1193–1200, 2004
Dursun A, Akyurek N, Gunel N, et al: Prognostic implication of nm23-H1 expression in colorectal carcinomas. Pathology 34: 427–432, 2002
Dusonchet L, Corsale S, Migliavacca M et al: Nm23-Hl expression does not predict clinical survival in colorectal cancer patients. Oncol Rep 10: 1257–1263, 2003
Royds JA, Cross SS, Silcocs PB, et al: Nm23-H1 “anti-metastatic” gene product expression in colorectal carcinoma. J Pathol 172: 261–266, 1994
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Elagoz, S., Egilmez, R., Koyuncu, A. et al. The intratumoral microvessel density and expression of bFGF and nm23-Hl in colorectal cancer. Pathol. Oncol. Res. 12, 21–27 (2006). https://doi.org/10.1007/BF02893427
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DOI: https://doi.org/10.1007/BF02893427