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首页> 外文期刊>Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association >Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia.
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Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia.

机译:胰腺癌或高度不典型增生患者的十二指肠胰液十二指肠样本中的突变型TP53。

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摘要

Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated whether mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer.We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls.TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions.We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701.
机译:影像学检查可以识别出胰腺肿瘤性囊肿,但不能发现显微镜下的不典型增生。我们调查了在分泌素刺激的胰液的十二指肠样本中是否可以检测到突变型TP53,以及该测定法是否可以用于筛查高度不典型增生和浸润性胰腺癌。我们确定了突变型TP53在微解剖的胰腺上皮内瘤变中的患病率( PanIN),导管内乳头状黏液性肿瘤(IPMN)和浸润性腺癌。 TP53突变是通过数字高分辨率熔体曲线分析和分泌素刺激的胰腺液样品测序而定量的,这些样品是从参与胰腺癌筛查试验的180位受试者的十二指肠收集的;由于家族性和/或遗传性胰腺癌易感性或作为对照而入组患者。在9.1%的中级IPMN中(22个中的2个),PanIN-2的17.8%(45个中的8个),38.1个中发现了TP53突变高档IPMN的百分比(21个中的8个),PanIN-3中的47.6%(21个中的10个)和浸润性胰腺腺癌的75%(20个中的15个);在PanIN-1病变或低级别IPMN中未发现TP53突变。在43例胰导管腺癌患者中的29例胰液十二指肠样本中检测到TP53突变(敏感性为67.4%; 95%置信区间为0.52-0.80)和8例高度病变(PanIN-3和高IPMN)。在58位对照或55位筛查个体中未发现晚期病变的样本中未发现TP53突变。我们在从高度不典型增生或浸润性胰腺癌患者的十二指肠收集的促胰液素刺激的胰腺液样本中检测到TP53突变。可能会开发出针对突变型TP53的测试,以改善对胰腺癌和高度不典型增生的诊断和筛查。临床试验编号:NCT00438906和NCT00714701。

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