大肠高、中分化腺癌临床特点、遗传不稳定性、TP53与KRAS基因突变的差异比较  

Comparison on Clinicopathological Features, Genetic Instability, TP53 and KRAS Gene Mutations between Well and Moderately Differentiated Colorectal Adenocarcinoma

作　　者：赵岩[1] 郑志超[1] 挂地吉弘[2] 冲英次 张涛[1] 张剑军[1] 赵宜良[1] 前原喜彦[2] 

机构地区：[1]辽宁省肿瘤医院第三外科,辽宁沈阳110042 [2]九州大学大学院医学研究院消化器综合外科

出　　处：《现代生物医学进展》2010年第6期1061-1064,共4页Progress in Modern Biomedicine

摘　　要：目的:近年来大肠中分化腺癌检出比例有所增高。本研究旨在探讨大肠中分化腺癌临床病理学及分子遗传学特征。方法:回顾过去30年1073例大肠癌的病理分型,比较其中328例高、中分化腺癌临床病理学特点。激光细胞学扫描技术,双荧光高分辨率微卫星不稳定性技术评价129例大肠癌遗传不稳定性特点,TP53、KRAS基因突变采用直接测序法检测。结果:由1979年始每10年为1组,至2008年计3组。中分化腺癌所占比例分别为37%、38%及55%。其中的328例大肠癌高、中分化腺癌病理学研究表明,中分化者较高分化者病期晚、浸润深、淋巴结转移率高、静脉侵袭阳性率高。对74例高分化腺癌与55例中分化腺癌的分子遗传学研究表明,高、中分化腺癌的DNA倍体与微卫星不稳定性情况无显著性差异,TP53与KRAS基因突变频率也无显著差异。但TP53的移码突变仅在高分化腺癌中检出(4例,P<0.05)。KRAS的颠换突变在高分化癌中检出5例(23%),在中分化癌中检出12例(57%),差异有显著性意义(P<0.05)。结论:高、中分化腺癌在临床病理学特征方面存在明显差异。大肠中分化腺癌较高分化腺癌生物学行为差,发现时病期较晚,治疗随访中需要引起足够重视。两种病理学类型的肿瘤遗传不稳定性急基因突变频率等背景相似,但基因突变谱的差别提示两种腺癌的发生背景的不同。Objective： This study is to evaluate the differences of clinicopathological and genetic features between well and moderately differentiated colorectal adenocarcinoma. Methods： A total of 1073 colorectal carcinoma cases were retrospectively reviewed to show the ratio of well and moderately differentiated adenocarcinoma in a timely fashion. The clinicopathological features of 328 well or moderately differentiated adenocarcinoma cases were evaluated. In 129 cases, Laser Scanning Cytomertery was used to assess DNA ploidy, the microsatellite instability status were studied by High Resolution Fluorescent Microsatellite Analysis assay. Mutation hotspots of TP53 and KRAS genes were directly sequenced. Results： The ratio of moderate differentiated adenocarcinoma in all pathology types was increased in the recent decade. Comparing with well differentiated adenocarcinoma, the moderately differentiated carcinoma showed more invasive characteristics, such as late stage, deeper infiltration, higher lymphatic metastatic rate, stronger vein invasion （P〈0.05）. The genetic instability patterns reflected by DNA aneuploidy or microsatellite instability of the well and moderately differentiated carcinoma were similar. The mutation rates of TP53 and KRAS genes were similar. However, frameshift mutation of TP53 was detected only in well differentiated adenocarcinoma; the frequency of trasversion mutations of KRAS were significantly higher in moderately differentiated adenocarcinoma. Conclusions：TRAIL and docetaxel have synergistlic killing effects on nasopharyngeal carcinoma CNE2 cells, which has a promising prospect in the treatment ofnasopharyngeal carcinoma.

关 键 词：大肠癌 高分化腺癌 中分化腺癌 遗传不稳定性 突变 

分 类 号：R735.34[医药卫生—肿瘤]