Kuno Toru, Tsukui Yuya, Takano Shinichi, Maekawa Shinya, Yamaguchi Tatsuya, Yoshida Takashi, Kobayashi Shoji, Iwamoto Fumihiko, Ishida Yasuaki, Kawakami Satoshi, Tanaka Keisuke, Fukasawa Yoshimitsu, Muraoka Masaru, Fukasawa Mitsuharu, Shindo Hiroko, Inoue Taisuke, Nakayama Yasuhiro, Mochizuki Kunio, Sato Tadashi, Enomoto Nobuyuki
First Department of Internal Medicine, Faculty of Medicine University of Yamanashi Chuo Japan.
Department of Gastroenterology Koyo Hospital Hokuto Japan.
JGH Open. 2019 Jun 25;4(1):75-82. doi: 10.1002/jgh3.12220. eCollection 2020 Feb.
Genetic indicators of endoscopic resection for colorectal carcinoma remain inconclusive. This study analyzed genetic changes in early colorectal tumors that could inform decisions for endoscopic procedures.
A total of 83 colorectal tumors from 81 patients, including adenoma ( = 7), Tis-T1a ( = 22), T1b ( = 14), and advanced carcinoma ( = 40), were analyzed. Tis tumors ( = 16) and some T1 carcinomas ( = 11) were analyzed as mixed adenomas and carcinomas. Lesions were laser-capture microdissected for DNA extraction, and targeted sequencing of 50 cancer-related genes was performed. Genetic data were then correlated with clinical records, including magnifying endoscopic findings.
Numbers of gene alteration rates in and increased with tumor progression from adenoma to carcinoma. Frequencies of mutant variants in ( = 0.004) and rates of copy number loss in ( = 0.006) increased in carcinoma components of mixed tumors compared to adenoma components. Moreover, adenoma components of T1b carcinomas had higher mutation rates than Tis or T1a carcinomas ( = 0.011) and pure adenomas ( = 0.026). Gene alterations in ( = 0.0055) and ( = 0.0055) increased in cases with irregular surface patterns of magnifying endoscopic findings.
Numbers of copy number variations and and alterations were related to colorectal tumor progression. alteration rates in adenoma components were high in T1b carcinomas, warranting complete treatment with en bloc resection. Magnifying endoscopic findings might reflect the genetic status of colorectal tumors.
结直肠癌内镜切除的遗传指标仍无定论。本研究分析了早期结直肠肿瘤的基因变化，可为内镜手术决策提供依据。
对81例患者的83个结直肠肿瘤进行分析，包括腺瘤（n = 7）、Tis-T1a（n = 22）、T1b（n = 14）和进展期癌（n = 40）。Tis肿瘤（n = 16）和部分T1癌（n = 11）作为混合腺瘤和癌进行分析。对病变进行激光捕获显微切割以提取DNA，并对50个癌症相关基因进行靶向测序。然后将基因数据与临床记录相关联，包括放大内镜检查结果。
从腺瘤到癌，肿瘤进展过程中APC和TP53基因改变率的数量增加。与腺瘤成分相比，混合肿瘤的癌成分中KRAS突变变体频率（n = 0.004）和CDKN2A拷贝数丢失率（n = 0.006）增加。此外，T1b癌的腺瘤成分比Tis或T1a癌（n = 0.011）和纯腺瘤（n = 0.026）具有更高的KRAS突变率。放大内镜检查结果显示表面不规则的病例中，NRAS（n = 0.0055）和BRAF（n = 0.0055）基因改变增加。
拷贝数变异数量以及APC和TP53改变与结直肠肿瘤进展相关。T1b癌的腺瘤成分中KRAS改变率较高，需要整块切除进行彻底治疗。放大内镜检查结果可能反映结直肠肿瘤的基因状态。
