BACKGROUND/AIMS: Oxidative stress is one of the causative agents of carcinogenesis. The DNA repair protein: MYH, NTH1 and MTH1 eliminate the oxidative DNA damage. In various tumors, overexpression of MTH1 has been reported. This is the first report demonstrating the expression of those proteins in colorectal cancer. METHODOLOGY: We investigated the expression of MYH, NTH1 and MTH1 by immunohistochemical typing methods in colorectal cancers obtained from consecutive patients undergoing surgery at the University of Tokyo hospital. RESULTS: High MYH immunoreactivity was detected in 57% of cases (46/81), which showed a significant correlation with the depth of tumor (p=0.04). Cytoplasmic expression of NTH1 was detected in 35% of cases (28/81), which showed a significant correlation with lymph node metastasis (p=0.001), histological grade according to the Dukes' Classification (p=0.005), and disease-free survival (p=0.04). High MTH1 immunoreactivity was detected in 84% of cases (68/81), which showed a significant correlation with tumor location (p=0.04). CONCLUSIONS: The expression pattern of DNA repair protein for oxidative DNA damage showed a significant correlation with aggressive features of colorectal cancer such as the depth of tumor, and lymph node metastasis, as well as with Dukes' classification and disease-free survival.
BACKGROUND/AIMS: Oxidative stress is one of the causative agents of carcinogenesis. The DNA repair protein: MYH, NTH1 and MTH1 eliminate the oxidative DNA damage. In various tumors, overexpression of MTH1 has been reported. This is the first report demonstrating the expression of those proteins in colorectal cancer. METHODOLOGY: We investigated the expression of MYH, NTH1 and MTH1 by immunohistochemical typing methods in colorectal cancers obtained from consecutive patients undergoing surgery at the University of Tokyo hospital. RESULTS: High MYH immunoreactivity was detected in 57% of cases (46/81), which showed a significant correlation with the depth of tumor (p=0.04). Cytoplasmic expression of NTH1 was detected in 35% of cases (28/81), which showed a significant correlation with lymph node metastasis (p=0.001), histological grade according to the Dukes' Classification (p=0.005), and disease-free survival (p=0.04). High MTH1 immunoreactivity was detected in 84% of cases (68/81), which showed a significant correlation with tumor location (p=0.04). CONCLUSIONS: The expression pattern of DNA repair protein for oxidative DNA damage showed a significant correlation with aggressive features of colorectal cancer such as the depth of tumor, and lymph node metastasis, as well as with Dukes' classification and disease-free survival.
Authors: Sang Soo Hah; Janna M Mundt; Hyung M Kim; Rhoda A Sumbad; Kenneth W Turteltaub; Paul T Henderson Journal: Proc Natl Acad Sci U S A Date: 2007-06-25 Impact factor: 11.205
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