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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: In recent years, the detection rate of differentiated adenocarcinoma of the large intestine has increased. This study aimed to investigate the clinical pathology and molecular genetics of differentiated adenocarcinomas in the large intestine. Methods: The pathological types of 1073 cases of colorectal cancer in the past 30 years were retrospectively reviewed, and the clinical and pathological features of 328 cases of high and moderately differentiated adenocarcinomas were compared. Laser cytology and double fluorescence high-resolution microsatellite instability were used to evaluate the genetic instability of 129 colorectal cancer patients. The mutations of TP53 and KRAS gene were detected by direct sequencing. Results: From 1979, every 10 years for a group, to 2008, totaling 3 groups. The proportion of differentiated adenocarcinoma was 37%, 38% and 55% respectively. Pathological studies of 328 cases of high and moderately differentiated adenocarcinoma of colorectal cancer showed that patients with moderately differentiated tumors had later stages of disease, deep invasion, high rate of lymph node metastasis and high rate of venous invasion. 74 cases of well-differentiated adenocarcinoma and 55 cases of moderately differentiated adenocarcinoma molecular genetic studies have shown that high and moderately differentiated adenocarcinoma of DNA ploidy and microsatellite instability did not differ significantly, TP53 and KRAS gene mutation frequency No significant difference. However, the frameshift mutation of TP53 was only detected in well-differentiated adenocarcinoma (4 cases, P <0.05). The transversion of KRAS was detected in 5 cases (23%) of well-differentiated cancers and in 12 (57%) of moderately-differentiated cancers, the difference was statistically significant (P <0.05). Conclusion: There are significant differences in clinicopathological characteristics between high and moderately differentiated adenocarcinomas. Differentiation of colorectal adenocarcinoma of high differentiated adenocarcinoma biological behavior is poor, when found late disease, the treatment of follow-up need to pay enough attention. The backgrounds of these two pathological types of tumors are similar, but the gene mutation profiles suggest different backgrounds of the two adenocarcinomas.