本文關(guān)鍵詞： 超聲內(nèi)鏡 高分辨熔解曲線 胃腸間質(zhì)瘤 KIT基因 血小板源性生長(zhǎng)因子受體α基因　出處：《浙江大學(xué)》2013年博士論文　論文類型：學(xué)位論文

【摘要】：目的： 胃腸間質(zhì)瘤(GISTs)是一種有潛在惡性的黏膜下腫瘤,很難做到術(shù)前確診。組織學(xué)表現(xiàn)和免疫組化結(jié)果仍然是GISTs診斷的金標(biāo)準(zhǔn)�；蛲蛔儥z測(cè)對(duì)于GISTs的治療有指導(dǎo)性意義。超聲內(nèi)鏡(EUS)是診斷胃腸道間質(zhì)瘤的最常用的工具。高分辨熔解曲線分析技術(shù)(HRM)是在實(shí)時(shí)熒光PCR基礎(chǔ)上發(fā)展起來(lái)的一種新的突變掃描和基因分型的遺傳分析技術(shù),具有高通量、簡(jiǎn)單、快速、低成本、高靈敏度的優(yōu)點(diǎn)。本研究旨在探討EUS在術(shù)前診斷GISTs的作用,以及HRM在檢測(cè)GISTs基因突變中的作用。 方法： 入選超聲內(nèi)鏡診斷為胃黏膜下病變,且最終取得病理確診的患者,根據(jù)超聲內(nèi)鏡結(jié)果和病理結(jié)果比較超聲內(nèi)鏡對(duì)GISTs的診斷的敏感性、特異性和準(zhǔn)確性。對(duì)小于2cm無(wú)EUS危險(xiǎn)特征的胃GISTs患者進(jìn)行EUS隨訪,了解小GISTs的發(fā)展特征,探討EUS對(duì)小GISTs的隨訪價(jià)值。對(duì)部分術(shù)后GISTs再行組織學(xué)和免疫組化的檢測(cè),了解GISTs的危險(xiǎn)分級(jí)和生物學(xué)特征。再用HRM檢測(cè)GISTs的基因突變情況,并與DNA測(cè)序相比較,分析HRM在檢測(cè)GISTs基因突變中的作用。 結(jié)果： 本研究中共63位胃黏膜下病變的患者參與評(píng)估,39例患者經(jīng)病理確診GISTs,平均年齡為：54.4±11.1歲,中位年齡54歲。超聲內(nèi)鏡診斷胃間質(zhì)瘤的敏感性為100%,特異性為45.8%,陽(yáng)性預(yù)測(cè)值為75%,陰性預(yù)測(cè)值為100%。參與EUS隨訪的29例GIST患者首發(fā)平均年齡為51.8±10.7歲,中位年齡52歲。29例GISTs經(jīng)過(guò)平均22±16.0月的隨訪,未發(fā)現(xiàn)腫瘤有明顯增大。11例胃GISTs再次用新標(biāo)準(zhǔn)進(jìn)行了病理評(píng)估,CD117和DOG-1均為陽(yáng)性,其中極低危1例,低危5例,中危3例,高危2例。有3例Ki-67在5-10%的患者均為中高危GISTs。12例GISTs的新鮮冰凍組織參與了基因突變的檢測(cè),其中有10例存在突變,9例胃GISTs突變發(fā)生在KIT基因第11外顯子的突變熱點(diǎn)區(qū),1例小腸GIST的突變發(fā)生在KIT基因第9外顯子。HRM對(duì)GISTs的KIT基因和PDGFRA基因外顯子突變檢測(cè)的敏感性、特異性和準(zhǔn)確性達(dá)到100%�；蛲蛔兊念愋团cGISTs的危險(xiǎn)程度無(wú)關(guān)。 結(jié)論： (1)超聲內(nèi)鏡可以分辨胃壁各層次和胃壁占位的內(nèi)部性質(zhì),診斷胃間質(zhì)瘤敏感性高,具有易操作,無(wú)放射性的優(yōu)點(diǎn),是診斷胃間質(zhì)瘤的首選方法。 (2)最大直徑2cm且無(wú)高危EUS特征的胃間質(zhì)瘤可以用超聲內(nèi)鏡進(jìn)行隨訪,間隔時(shí)間推薦為1-1.5年。 (3)Ki-67陽(yáng)性程度與GISTs的危險(xiǎn)程度相關(guān),或許能成為預(yù)后檢測(cè)指標(biāo)。 (4)HRM對(duì)GISTs基因突變檢測(cè)的敏感性、特異性和準(zhǔn)確性均較高。是一種適合臨床診斷的基因突變檢測(cè)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 鹵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 鹵10.7 years old. A median age of 52 years. 29 cases of GISTs were followed up for an average of 22 鹵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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R443.8

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