Chromosomal instability evidenced by a loss of heterozygosity (LOH) is implicated as a predictor of poor survival in patients with colorectal cancer, whereas microsatellite instability (MSI) is associated with improved survival rates. We investigated the relationship between tumor expression of angiogenic growth factors and genomic alterations in colorectal cancer.
Two genotypes, LOH and MSI, determined by microsatellite markers in the 4 cancer-related chromosomes 2p, 3p, 17p, and 18q, were analyzed in 73 patients with colorectal cancer. The tumor-specific expression of vascular endothelial growth factor and hepatocyte growth factor (HGF) were quantified, and the interleukin-6 network also was evaluated.
MSI-positive neoplasms showed a lesser expression of both tumor growth factors and interleukin-6. In contrast, LOH-positive neoplasms showed a greater expression of HGF and a lesser expression of interleukin-1–receptor antagonist. MSI neoplasms were correlated with favorable prognosis in agreement with previous findings.
The suppressed production of angiogenic growth factors in MSI cancers partly might explain the better prognosis in MSI-positive patients. The interleukin-6 network, which upregulates production of vascular endothelial growth factor and HGF, might be involved in this mechanism.
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- Molecular genetics and ethnic factors in the genetic pathogenesis of colorectal cancer.Ann NY Acad Sci. 2000; 910: 50-61
- Microsatellite instability and the clinicopathological features of sporadic colorectal cancer.Gut. 2001; 48: 821-829
- Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability.Cancer. 2000; 89: 2025-2037
- Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis.Nature. 1993; 363: 558-561
- Microsatellite instability and the role of hMSH2 in sporadic colorectal cancer.Oncogene. 1996; 12: 2641-2649
- Microsatellite instability in sporadic-colon-cancer patients with and without liver metastases.Int J Cancer. 1997; 74: 470-474
- Genetic classification of colorectal cancer based on chromosomal loss and microsatellite instability predicts survival.Clin Cancer Res. 2002; 8: 2311-2322
- Survival and acquired genetic alterations in colorectal cancer.Gastroenterology. 1992; 102: 1136-1141
- Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers.J Natl Cancer Inst. 1999; 91: 1295-1303
- Allelic loss of chromosome 18q and prognosis in colorectal cancer.N Engl J Med. 1994; 331: 213-221
- Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma.Int J Cancer. 1997; 74: 545-550
- Factors influencing tissue concentration of vascular endothelial growth factor in colorectal carcinoma.Am J Gastroenterol. 2000; 95: 1062-1067
- Genomic instability in colorectal carcinomas.J Pathol. 1996; 179: 15-19
- Angiogenic factor VEGF is decreased in human colorectal neoplasms showing DNA microsatellite instability.J Pathol. 1999; 189: 319-335
- Serum hepatocyte growth factor as an index of disease status of patients with colorectal carcinoma.Br J Cancer. 1988; 78: 454-459
- Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis.Clin Exp Metastasis. 2000; 18: 639-649
- Molecular cloning and expression of human hepatocyte growth factor.Nature. 1989; 342: 440-443
- The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells.J Cell Biol. 1993; 121: 145-154
- Regulation of vascular endothelial growth factor expression in human colon cancer by interleukin-1 beta.Br J Cancer. 1999; 80: 1506-1511
- The role of interleukin-1 beta in the pathogenesis of multiple myeloma.Hematol Oncol Clin North Am. 1999; 13: 1117-1125
- Interleukin-1 regulates interleukin-6 secretion in human oral squamous cell carcinoma in vitro.Cancer Res. 1998; 58: 3142-3149
- Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas.Nature. 1988; 332: 83-85
- Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas.FEBS Lett. 1989; 250: 607-610
- Intra-tumoral interleukin-6 down-regulation system and genetic mutations of tumor suppressor genes in colorectal carcinoma.Cancer. 2002; 94: 1584-1592
- A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition.Cancer Res. 1998; 58: 5248-5257
- Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo.Am J Pathol. 2001; 158: 1111-1120
- Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells.Br J Pharmacol. 2003; 140: 595-610
- Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma.Cancer. 2004; 100: 270-278
- Cytokines facilitate chemotactic motility of breast carcinoma cells.Breast Cancer. 2000; 7: 221-230
- Serum interleukin-6 levels reflect the disease status of colorectal cancer.J Surg Oncol. 2003; 83: 222-226
- Recombinant human interleukin-6 induces hepatocyte growth factor production in cancer patients.Scand J Gastroenterol. 2001; 36: 636-640
- Growth control of human biliary epithelial cells by interleukin 6, hepatocyte growth factor, transforming growth factor beta 1, and activin A.Hepatology. 2000; 32: 26-35
- A two-way interaction between hepatocyte growth factor and interleukin-6 in tissue invasion of lung cancer cell line.Am J Respir Cell Mol Biol. 2002; 27: 220-226
- Vascular endothelial growth factor expression in early stage ovarian carcinoma.Cancer. 1997; 80: 98-106
- Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer.Br J Cancer. 2002; 87: 1437-1444
- Reciprocal relationship between the tumor suppressors p53 and BAX in primary colorectal cancers.Oncogene. 1998; 17: 2003-2008
- Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression.Cancer Res. 1995; 55: 6161-6165
Accepted: August 16, 2005
Received in revised form: July 28, 2005
Received: January 25, 2005
© 2006 Mosby, Inc. Published by Elsevier Inc. All rights reserved.