胃型ならびに腸型分化型腺癌の遺伝子変化

Genetic Analysis of Differentiated-type Adenocarcinomas of the Stomach with Gastric Phenotype and Intestinal Phenotype

要旨　胃分化型腺癌を細胞形質で，①極めてよく胃腺窩上皮型の細胞形質を有する群，②極めてよく完全型腸上皮化生型の細胞形質を有する群，そして③通常型の分化型腺癌群，に分類し，各群におけるp53，APC，K-ras遺伝子変異およびmicrosatellite instabihty（MSI）の頻度を検索した．p53遺伝子変異率は①群で5％（1/22），②群で31％（4/13），③群で18％（3/17）であった．APC遺伝子変異は①群で9％（2/22），③群で6％（1/17）認められた．K-ras遺伝子変異は3群のいずれにも検出されなかった．一方，MSIは①群で45％（10/22），②群で0％，③群で24％（4/17）と，①群と②群とでは極めて対照的な結果であった（p＜0.01）．以上の結果から，胃分化型腺癌の遺伝子的発生経路はその細胞形質によって大きく異なっており，腺窩上皮型分化型腺癌ではMSIの関与が大きく（mutator pathway），完全型腸上皮化生型分化型腺癌ではp53遺伝子の関与が大きいこと（suppressor pathway）が示唆された．これらの結果は胃分化型腺癌の組織発生の多様性を反映しているものと思われた．

　Genetic pathways of colorectal carcinoma have been elucidated, but those of gastric carcinoma are still unclear. In differentiatedtype gastric carcinomas, some phenotypical variations are known, i.e., gastric phenoty-pe and intestinal phenotype. It is speculated that they have different histological backgrounds in the tumorigenesis. To investigate the relationship between genetic alterations and phenotypes of differentiated-type carcinoma, we analyzed mutations of p53, APC, and K-ras genes, and microsatellite instability (MSI) as they were found in differentiated gastric carcinomas with extremely well-preserved gastric foveolar phenotype (foveolar-type), complete-type intestinal metaplastic phenotype (CIM-type), and ordinary-type. MSI was detected in 10 out of 22 (45%) of foveolar-type and 4 out of 17 (24%) of ordinary-type, while no MSI was detected in CIM-type. p53 alterations were detected in 4 out of 13 (31%) of CIM-type, 18% of ordinary-type, and 5% of foveolar-type. APC gene alterations were detected in two cases of foveolar-type and one case of ordinary-type. No K-ras gene mutation was detected in any of these three types. These results indicate that genetic pathways are quite different in each phenotype. Taking the phenotypes into account will be vital in elucidating the genetic pathways of gastric carcinoma.