Genomic instability and tissue expression of angiogenic growth factors in sporadic colorectal cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
Yasuhiro
Y
Inoue
Chikao
C
Miki
Hideki
H
Watanabe
Eiki
E
Ojima
Masato
M
Kusunoki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor