超声内镜与高分辨熔解曲线分析技术对胃肠间质瘤的诊断作用

发布时间：2018-03-01 07:38

  本文关键词： 超声内镜 高分辨熔解曲线 胃肠间质瘤 KIT基因 血小板源性生长因子受体α基因　出处：《浙江大学》2013年博士论文　论文类型：学位论文

【摘要】：目的： 胃肠间质瘤(GISTs)是一种有潜在恶性的黏膜下肿瘤,很难做到术前确诊。组织学表现和免疫组化结果仍然是GISTs诊断的金标准。基因突变检测对于GISTs的治疗有指导性意义。超声内镜(EUS)是诊断胃肠道间质瘤的最常用的工具。高分辨熔解曲线分析技术(HRM)是在实时荧光PCR基础上发展起来的一种新的突变扫描和基因分型的遗传分析技术,具有高通量、简单、快速、低成本、高灵敏度的优点。本研究旨在探讨EUS在术前诊断GISTs的作用,以及HRM在检测GISTs基因突变中的作用。 方法： 入选超声内镜诊断为胃黏膜下病变,且最终取得病理确诊的患者,根据超声内镜结果和病理结果比较超声内镜对GISTs的诊断的敏感性、特异性和准确性。对小于2cm无EUS危险特征的胃GISTs患者进行EUS随访,了解小GISTs的发展特征,探讨EUS对小GISTs的随访价值。对部分术后GISTs再行组织学和免疫组化的检测,了解GISTs的危险分级和生物学特征。再用HRM检测GISTs的基因突变情况,并与DNA测序相比较,分析HRM在检测GISTs基因突变中的作用。 结果： 本研究中共63位胃黏膜下病变的患者参与评估,39例患者经病理确诊GISTs,平均年龄为：54.4±11.1岁,中位年龄54岁。超声内镜诊断胃间质瘤的敏感性为100%,特异性为45.8%,阳性预测值为75%,阴性预测值为100%。参与EUS随访的29例GIST患者首发平均年龄为51.8±10.7岁,中位年龄52岁。29例GISTs经过平均22±16.0月的随访,未发现肿瘤有明显增大。11例胃GISTs再次用新标准进行了病理评估,CD117和DOG-1均为阳性,其中极低危1例,低危5例,中危3例,高危2例。有3例Ki-67在5-10%的患者均为中高危GISTs。12例GISTs的新鲜冰冻组织参与了基因突变的检测,其中有10例存在突变,9例胃GISTs突变发生在KIT基因第11外显子的突变热点区,1例小肠GIST的突变发生在KIT基因第9外显子。HRM对GISTs的KIT基因和PDGFRA基因外显子突变检测的敏感性、特异性和准确性达到100%。基因突变的类型与GISTs的危险程度无关。 结论： (1)超声内镜可以分辨胃壁各层次和胃壁占位的内部性质,诊断胃间质瘤敏感性高,具有易操作,无放射性的优点,是诊断胃间质瘤的首选方法。 (2)最大直径2cm且无高危EUS特征的胃间质瘤可以用超声内镜进行随访,间隔时间推荐为1-1.5年。 (3)Ki-67阳性程度与GISTs的危险程度相关,或许能成为预后检测指标。 (4)HRM对GISTs基因突变检测的敏感性、特异性和准确性均较高。是一种适合临床诊断的基因突变检测方法。
[Abstract]:Objective:. Gastrointestinal stromal tumors (GISTs) are potentially malignant submucosal tumors. Histologic findings and immunohistochemical results are still the gold standard for the diagnosis of GISTs. The detection of gene mutation is instructive for the treatment of GISTs. EUS is the most commonly used method in the diagnosis of gastrointestinal stromal tumors (GIST). HRM is a new mutation scanning and genotyping genetic analysis technique developed on the basis of real-time fluorescent PCR. This study was designed to investigate the role of EUS in the preoperative diagnosis of GISTs and the role of HRM in the detection of GISTs gene mutations. Methods:. The sensitivity of endoscopic ultrasonography to the diagnosis of GISTs was compared according to the results of endoscopy and pathology in patients with submucosal lesions of stomach. Specificity and accuracy. EUS follow-up was performed in patients with gastric GISTs with no risk of EUS at less than 2 cm, to understand the developmental characteristics of small GISTs, to explore the value of EUS in the follow-up of small GISTs, and to detect the histology and immunohistochemistry of GISTs after partial operation. To understand the risk classification and biological characteristics of GISTs, to detect the mutation of GISTs gene by HRM, and to analyze the role of HRM in the detection of GISTs gene mutation compared with DNA sequencing. Results:. In this study, a total of 63 patients with gastric submucosal lesions participated in the assessment of 39 patients with pathological diagnosis of GISTs.The average age was 54.4 卤11.1 years old. The median age was 54 years. The sensitivity, specificity, positive predictive value and negative predictive value of EUS in diagnosis of gastric stromal tumors were 100, 45.8, 75 and 100 respectively. The mean age of 29 patients with GIST following up with EUS was 51.8 卤10.7 years old. A median age of 52 years. 29 cases of GISTs were followed up for an average of 22 卤16.0 months. No significant enlargement of the tumor was found. 11 cases of gastric GISTs were again evaluated for CD117 and DOG-1 with the new criteria. Among them, 1 case was at very low risk, 5 cases were at low risk, and 3 cases were at middle risk. High risk 2 cases. 3 cases of Ki-67 in 5-10% of the patients were middle and high risk GISTs.12 cases of fresh frozen tissue of GISTs participated in the detection of gene mutation. There were 10 cases of gastric GISTs mutation occurred in the hot spot of exon 11 of KIT gene and 1 case of small intestinal GIST mutation occurred in KIT gene exon 9. HRM was sensitive to GISTs KIT gene and PDGFRA gene exon mutation. Specificity and accuracy were 100%. The type of gene mutation was not related to the risk of GISTs. Conclusion:. Ultrasound endoscopy can distinguish the internal properties of gastric wall and gastric wall occupying position. It has the advantages of high sensitivity, easy operation and no radioactivity in diagnosis of gastric stromal tumors. It is the first choice method for diagnosis of gastric stromal tumors (GIST). (2) gastric stromal tumors with a maximum diameter of 2 cm and no high risk EUS characteristics can be followed up by endoscopic ultrasonography. The interval is recommended to be 1-1.5 years. The positive degree of Ki-67 was correlated with the risk of GISTs and might be a prognostic marker. The sensitivity, specificity and accuracy of HRM for detection of GISTs gene mutation are high. It is a suitable gene mutation detection method for clinical diagnosis.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R443.8

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