Yamagata S, Muto T, Uchida Y, Masaki T, Higuchi Y, Sawada T, Hirooka T
First Department of Surgery, University of Tokyo, Japan.
Cancer. 1995 Feb 15;75(4):953-7. doi: 10.1002/1097-0142(19950215)75:4<953::aid-cncr2820750409>3.0.co;2-r.
To clarify genetic changes in colorectal tumorigenesis, K-ras codon 12 point mutations were examined in 101 ordinary colorectal carcinomas and 6 that complicated ulcerative colitis (UC) with special attention to growth patterns.
The depths of invasion of ordinary carcinoma were submucosa (SMCa) in 39 cases, muscularis propria (PMCa) in 33, and far-advanced in 29. Growth patterns of SMCa and PMCa were classified into three types: polypoid-growth type without central depression (Type 1), polypoid-growth type with central depression (Type 2), and nonpolypoid-growth type. DNA samples were extracted from formalin fixed paraffin embedded sections, and K-ras codon 12 mutations were examined by two-step polymerase chain reaction-restriction fragment length polymorphism.
K-ras mutation frequency was higher in Type 1 SMCa than in nonpolypoid SMCa, 56% (9/16) versus 6% (1/17), respectively, and in PMCa, 78% (7/9) versus 23% (3/13), respectively. In 6 UC carcinomas, a K-ras mutation was detected in only one polypoid carcinoma and none were detected in five nonpolypoid carcinomas.
These results and the authors' previous study suggest that nonpolypoid carcinomas may be derived from flat adenomas, whose K-ras mutation incidence also was low, and this pathway is different from a genetic model based on the ordinary adenoma-carcinoma sequence through polypoid adenomas.
为阐明结直肠癌发生过程中的基因变化，对101例普通结直肠癌和6例合并溃疡性结肠炎（UC）的病例进行了K-ras密码子12点突变检测，并特别关注其生长模式。
普通癌的浸润深度，39例为黏膜下层（SMCa），33例为固有肌层（PMCa），29例为进展期。SMCa和PMCa的生长模式分为三种类型：无中央凹陷的息肉样生长型（1型）、有中央凹陷的息肉样生长型（2型）和非息肉样生长型。从福尔马林固定石蜡包埋切片中提取DNA样本，通过两步聚合酶链反应-限制性片段长度多态性检测K-ras密码子12突变。
1型SMCa的K-ras突变频率高于非息肉样SMCa，分别为56%（9/16）和6%（1/17），在PMCa中分别为78%（7/9）和23%（3/13）。在6例UC癌中，仅在1例息肉样癌中检测到K-ras突变，5例非息肉样癌中均未检测到。
这些结果以及作者之前的研究表明，非息肉样癌可能来源于扁平腺瘤，其K-ras突变发生率也较低，且该途径不同于基于普通腺瘤-癌序列通过息肉样腺瘤的遗传模型。
