Morphology of sporadic colorectal cancer with DNA replication errors
Morphology of sporadic colorectal cancer with DNA replication errors
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DOI：
10.1136/gut.42.5.673
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发表时间：
1998-05-01
期刊：
影响因子：
24.5
通讯作者：
Leggett, B
中科院分区：
文献类型：
--
作者：
Jass, JR;Do, KA;Leggett, B
背景-高达15%的结直肠癌具有DNA微卫星不稳定性(MIN)的特征，表现为DNA复制错误(RERS)的存在。目的-识别具有广泛MIN的结直肠癌(CRC)的病理特征。对象-前瞻性的303例结直肠癌患者，无家族性腺瘤性息肉病或遗传性非息肉病结直肠癌家族史。方法从新鲜组织样本中提取DNA，在包括转化生长因子βRII、IGFIIR和Bax在内的9个基因座上研究MIN的存在。对61例显示RERS的病例和63例RER阴性的病例进行了一系列临床和病理变量的比较。结果：27例结直肠癌患者表现为广泛的RERS(3个或更多)(RER+)，34例仅有有限的RERS(28=1个基因座；6=2个基因座)(RER+/-)，呈双峰分布。RER+癌不同于RER-和RER+/-病例。肿瘤类型(腺癌、粘液癌和未分化癌)(p=0.001)、肿瘤浸润性淋巴细胞(p=0.001)和解剖部位(p=0.001)是最显著的判别变量。通过决策树分析开发的算法可以将病例分配到RER+与RER-和+/-状态，全局敏感度为81.5%，特异度为96%，总体准确率为93%。结论：结直肠癌病理检查可以分配RER+状态；分配具有特异性和相对敏感性。相反，RER-和RER+/-CRC是无法区分的。
Background-Up to 15% of colorectal cancers are characterised by DNA microsatellite instability (MIN), shown by the presence of DNA replication errors (RERs).Aims-To identify pathological features that are discriminating for colorectal cancer (CRC) showing extensive MIN.Subjects-A prospective series of 303 patients with CRC and no family history of either familial adenomatous polyposis or hereditary non-polyposis colorectal cancer.Methods-DNA was extracted from fresh tissue samples and the presence of MIN was studied at nine loci that included TGF beta RII, IGFIIR, and BAX. The 61 cases showing RERs were compared with 63 RER negative cases with respect to a comprehensive set of clinical and pathological variables. Predictive utility of the variables was tested by decision tree analysis.Results-Twenty seven patients with CRC showed extensive RERs (three loci or more) (RER+) and 34 had limited RERs only (28 = one locus; 6 = two loci) (RER+/-), yielding a bimodal distribution. RER+ cancers differed from RER-and RER+/- cases. Tumour type (adenocarcinoma, mucinous carcinoma, and undifferentiated carcinoma) (p=0.001), tumour infiltrating lymphocytes (p=0.001), and anatomical site (p=0.001) were the most significant of the discriminating variables. Algorithms developed by decision tree analysis allowed cases to be assigned to RER+ versus RER-and +/- status with a global sensitivity of 81.5%, specificity of 96%, and overall accuracy of 93%.Conclusion-Pathological examination of CRC allows assignment of RER+ status; assignment is specific and relatively sensitive. Conversely RER-and RER+/- CRC are indistinguishable.