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要旨 表面型早期大腸癌の特異性をみる目的で,K-ras遺伝子の異常を遺伝子産物の免疫染色とPCRを用いた点突然変異で検索し報告した.表面型大腸癌は腫瘍高を測定し,その高さでType ⅡAとⅡBに分け,それ以外の早期癌(Type Ⅰ)と分けて検討した.対象はいずれも分化型腺癌とした.結果は,免疫染色の反応陽性は腺腫で7/17(41%),typeⅠ 12/19(63%),Type ⅡA 4/10(40%),Type ⅡB 0/9,進行癌 5/11(45%)であり,K-ras codon 12における点突然変異率はそれぞれ,3/16(19%),7/16(44%),1/4(25%),0/8(0%),4/11(36%)であった.この結果から進行癌に至る経路にはras遺伝子の異常を伴わない発癌機序があることが類推された.また,Type ⅡB とした平坦陥凹型を呈する分化型腺癌例では全例,rasの異常を示した症例はなかった.
To evaluate the specificity of carcinogenesis of superficial cancer in comparison with cancer arising from the adenoma-carcinoma sequence, we conducted immunohistochemical study on ras oncogene product and the point mutations in codon 12 of the Ki-ras gene in superficial cancer. It is already confirmed that the activation of ras gene is involved in initial stage of carcinogenesis of adenoma-carcinoma sequence.
Results was as follows: (1) Immunohistochemical staining showed an expression of ras gene product in 40% of the cases with adenoma, 60% of the cases with early cancer of non-superficial type, and 44% of the cases with advanced cancer. No positive reaction was seen in any cases of well differentiated flat depressed subtype of superficial type. (2) Cases of Type ⅡA including adenoma displayed reactions almost similar to those of the cases with non-superficial type (60%). Reaction was also positive in 20% of the cases with Type ⅡA which did not included adenoma. (3) The proportions of point mutation in codon 12 of the K-ras gene were 19%, 44%, 36%, 25% in adenoma, Type Ⅰ cancer, advanced cancer, and Type ⅡA cancer, respectively. No point mutations occurred in Type ⅡB cancer or normal large bowel tissue obtained from colorectal cancer patients.
To evaluate the specificity of the development process of superficial type carcinoma, the point mutation in codon 12 of Ki-ras gene and immunohistochemical staining of ras gene product were investigated. It was indicated that there exists process different from carcinogenesis of adenoma-carcinoma sequence in superficial colorectal cancer (Type ⅡB).
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