| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Research Abstract |
Recent advances in colonoscopic techniques have resulted in more frequent detection of superficial-type colorectal tumors, i.e., laterally spreading tumors (LSTs), although little is known about the characteristic clinical features and genetic alterations of LSTs. To elucidate the molecular characteristics of LSTs, genetic alterations in the KRAS, BRAF, and PIK3CA genes and abnormal expression of the p53, β-catenin, and MYC proteins were analysed using direct DNA sequencing and immunohistochemistry for 50 protruded type tumors (Protruded), 35 granular-type LSTs (LST-G) and 19 non-granular-type LSTs (LST-NG). In addition, loss of heterozygosity (LOH) close to the adenomatous polyposis coli (APC) gene (5q21) was examined in these tumors. In univariate analyses, significant differences were noted in the percentages with KRAS mutations (LST-G, LST-NG=54.3%, 21.1%, respectively, p=0.016), nuclear accumulation of β-catenin (LST-G, LST-NG=37.1%, 68.4%, respectively, p=0.027), and LOH at the APC gene locus (LST-G, LST-NG=28.0%, 60.0%, respectively, p=0.030). Multivariate analysis demonstrated that the macroscopic subtype of LST was significantly associated with KRAS mutation (for LST-NG : odds ratio [OR] 0.222, 95% CI 0.056-0.883) and nuclear accumulation of β-catenin (for LST-NG : OR 4.512, 95% CI 1.124-18.11). Our data revealed that the two subtypes of LST have different molecular characteristics, suggesting that two or more different molecular mechanisms result in colorectal tumors with a similar growth pattern.
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