c-kit基因突变对胃肠道间质瘤预后的影响

目的　探讨c kit基因突变与胃肠道间质瘤 (GIST)临床病理指标和预后的关系 ,为GIST恶性变判断、预后评估提供客观指标。方法　对 82例GIST患者运用聚合酶链反应 单链构象多态性分析、DNA测序的方法筛选c kit基因突变病例 ,采用统计学方法回顾性分析c kit癌基因突变与GIST临床病理特征、生物学行为、复发和病死率的关系。结果　c kit基因突变阳性组与c kit基因突变阴性组间肿瘤大小 (χ2 =16 795 ,P <0 0 1)、增殖细胞核抗原指数 (χ2 =17 0 99,P <0 0 1)、有丝分裂计数 (χ2 =11 2 33,P <0 0 1)、坏死 (χ2 =4 4 0 4 ,P <0 0 5 )、浸润 (χ2 =2 2 391,P <0 0 1)、复发 (χ2 =16 333,P <0 0 1)、转移 (χ2 =12 96 5 ,P <0 0 1)、死亡 (χ2 =11 6 4 6 ,P <0 0 1)差异有显著意义 ,而年龄 (χ2 =0 0 0 0 2 ,P >0 0 5 )、性别 (χ2 =0 14 1,P >0 0 5 )、肿瘤的部位 (χ2 =7 5 2 4 ,P >0 0 5 )、细胞类型 (χ2 =0 82 7,P >0 0 5 )、囊性变 (χ2 =1 6 0 8,P >0 0 5 )、出血 (χ2 =0 6 33,P >0 0 5 )、c kit蛋白表达 (χ2 =0 0 0 0 ,P >0 0 5 )差异无显著意义。结论　c kit基因突变的检测可作为GIST患者预后评估的有意义指标     

胃肠道间质瘤研究进展

胃肠道间质瘤 (gastrointestinalstromaltumors ,GISTs)是一种来源于胃肠道原始间质细胞的缺乏分化或未定向分化的非上皮性肿瘤 ,是消化道独立的一类间叶性肿瘤[1] 。近年来 ,国内外文献中对GISTs的组织发生、临床病理、免疫组化表型及超微结构变化、诊断及鉴别诊断、生物学行为等有较多报道 ,现综述如下 :1　GISTs的组织发生　　关于GISTs的组织学起源 ,目前尚无定论 ,最早认为其为平滑肌源性和神经源性肿瘤 ,后来研究发现它既非平滑肌 ,也非神经源性 ,而是来源于非定向分化的间充质细胞肿瘤。最近Kindblom等[1] 研究发现胃肠道蠕动…     

胃肠道间质瘤的特殊类型研究进展

胃肠道间质瘤是胃肠道非上皮源性常见肿瘤。由于该肿瘤在组织起源、生物学行为判断和免疫组化表型等方面仍然存在不同的意见和新的发现，已引起国内外学者的广泛关注。本文就胃肠道外间质瘤、胃肠道自主神经肿瘤、胃肠道间质瘤与神经纤维瘤病和其他上皮性肿瘤的临床关系和研究进展进行综述。     

胃肠道间质瘤诊治进展

胃肠道间质瘤是原发于胃肠道和腹腔的间叶细胞肿瘤,绝大多数存在ckit基因突变。即便是极低恶性,仍有复发的可能。外科手术切除仍是目前最有效的治疗方法。ckit特异性抑制剂甲磺酸伊马替尼是近年来分子靶向治疗的重大进步,改变了GIST的治疗现状。     

基因突变与胃肠道间质瘤研究进展

摘要：c kit及血小板源性生长因子受体α（platelet derived growth factor receptor alpha,PDGFRA）的功能增强性突变是导致胃肠道间质瘤（GIST）的主要原因。c kit基因及PDGFRA基因的突变位点及突变方式对肿瘤的临床特征有明显影响。笔者就基因突变与GIST的关系进行综述。     

胃肠间质瘤KIT和PDGFRA基因突变的检测和意义

目的 探讨中国胃肠间质瘤(GIST)患者KIT和血小板源性生长受体α(PDGFRA)基因突变的特点,分析其临床意义.方法 对136例GIST患者肿瘤组织进行DNA抽提、聚合酶链反应(PCR)扩增和直接测序,检测KIT基因外显子9、11、13、17和PDGFRA基因12、18外显子突变;并对8例取得伊马替尼耐药瘤组织的患者进行2次检测.结果 在136例患者中,KIT突变111例(81.6%).其中外显子11突变95例(69.8%),外显子9突变16例(11.8%),未检测到PDGFRA突变的病例.KIT和PDGFRA野生型25例(18.4%).KIT外显子11突变最常见为5'缺失突变,共60例(60/95,63.2%),其次为点突变21例(21/95,22.1%);KIT外显子9突变均为插入串联重复,其中14例(14/16,87.5%)为常见的密码子502和503重复,而另外2例为罕见的密码子501和502重复.不同性别、年龄以及晚期GIST患者和潜在恶性的GIST患者间突变情况差异无统计学意义(P＞0.05);而不同部位GIST的KIT外显子11突变发生率差异有统计学意义(P＜0.01).伊马替尼耐药GIST的检测中发现1例继发的KIT外显子17点突变(Asp820Val+Tyr823Asp).结论 KIT基因突变在中国GIST患者中常见,不同部位间KIT外显子11突变差异有统计学意义.KIT继发性突变发生于靶向药物伊马替尼耐药的患者.     

胃肠道间质瘤15例临床分析

胃肠道间质瘤(gastrointestinal stromal tumor,CIST) 是消化道原发性非上皮肿瘤,易于误诊,预后较差。今将收治15例报告如下。 1 临床资料 1.1 一般资料男9例,女10例,年龄38～83岁,平均年龄56．2岁,其中45岁以上12例(80％)。主要表现:呕血6 例(40％),黑便10例(66．7％),贫血12例(80％),恶心呕吐     

肝转移胃肠道间质瘤c-kit、PDGFRA基因突变研究

目的 探讨肝转移胃肠道间质瘤( GIST)发生的机制.方法 应用聚合酶链反应(PCR)和基因测序法检测12例肝转移GIST c-kit基因第9、11、13、17号外显子和PDGFRA第12、18号外显子序列,总结基因突变规律,分析其与临床病理的关系.结果 本组5例胃部,1例小肠,其他6例.本组c-kit基因突变率为91.7％ (11/12),外显子11为83.3％ (10/12).未检测到PDGFRA基因突变.本组性别、年龄、原发部位、肿瘤大小、核分裂相、NIH危险度分级、肝转移时间、细胞形态、细胞丰富程度、核异型对c-kit基因外显子11突变率及突变形式影响差异无统计学意义(P＜0.05).结论 肝转移GIST基因突变主要集中在c-kit第11号外显子.突变方式有缺失、点突变和缺失伴点突变.缺失突变多见.肝转移GIST临床病理与外显子11突变率、突变形式无明显相关.     

胃肠道间质瘤诊疗新进展

胃肠道与子宫一样是富于平滑肌的器官，因此，长期以来，胃肠道亦被认为同子宫一样是平滑肌肿瘤的好发部位。这种观点直至上世纪六十年代从未被怀疑过。然而，现在证明，这是医学上的一个历史性错误。当胃肠道间质瘤(gastrointestinal stromal tumors，GIST)的名称提出后，数十年来经过各学科尤其是病理学的不断研究和深入认识，     

胃肠道间质瘤的临床分析

目的探讨胃肠道间质瘤的临床诊断与治疗。方法回顾性分析95例胃肠道恶性间质瘤病人的临床资料。结果发生于胃、小肠、结直肠、肠系膜、大网膜的病例分别为65、25、2、2、1例；肿瘤直径1～10cm；其中恶性者47例，良性者48例；行根治性切除62例，行切除术31例，2例广泛转移者行肝结节活检。17例术后发生伤口感染，免疫组化指标：CD117、CD34、CK、EMA、S-100及Desmin阳性率分别为89．5％、86．3％、5．3％、0、9．5％及8．4％。随访80例，2例胃间质瘤广泛转移者分别于术后4月、6月死亡，17例术后5～25月死于其他疾病，余者均无瘤生存，5年生存率43．7％。结论提高对胃肠道间质瘤的认识，强化术中病理学检查及免疫组化检查，确定良恶性及恶性程度，采取合理规范的手术方式，对预后及防止复发有一定意义。     

胃肠道间质瘤

为分析胃肠道间质瘤（ＧＳＴ）的临床特点，对我院近８年来收治的３９例ＧＳＴ患者进行了回顾性分析。结果显示：本组病例平均发病年龄为４６岁，男２１例，女１８例。发生部位分布为：胃１５例（３８．５％），小肠１７例（４３．６％），十二指肠４例（１０．３％），结肠３例（７．７％）。３９例均经外科手术治疗，病理组织学显示良性３１例（７９．５％），不确定型５例（１２．８％），恶性３例（７．７％）。最常见的临床症状为胃肠出血，其中１０％的患者需紧急手术治疗。随访时间平均３年，随访期间６例患者死亡，３例死于与肿块无关的心脑疾患，７例复发，其中５例远处转移。７例局部复发或远处转移患者经再次或多次手术，配合化疗，４例存活或带瘤存活０．５～８年。结果表明：对此类肿瘤，手术宜扩大切除，术后密切随访。对复发或远处转移的病人，不要轻易放弃治疗，应持积极态度，经多次姑息切除，并辅以化疗，可望延长病人生存期。     

Impact of KIT and PDGFRA Gene Mutations on Prognosis of Patients with Gastrointestinal Stromal Tumors After Complete Primary Tumor Resection

Introduction  To investigate the impact of KIT and PDGFRA gene mutations on the prognosis of gastrointestinal stromal tumors (GIST). Material and Methods  Tumor tissue from 184 patients with primary GIST was submitted to mutational analysis of exons 9, 11, 13, and 17 of the KIT gene and exons 12 and 18 of the PDGFRA gene. Clinical and pathological parameters were analyzed and correlated to the risk of recurrence and disease-free survival (DFS). Results and Discussion  The authors found that somatic mutations were detected in 162 tumors (88.0%). Age, clinical stage, mitotic count, and tumor size were of prognostic relevance on both univariate and multivariate analysis. Five-year DFS was 41.9%. While the presence of a KIT or PDGFRA mutation per se was not associated with tumor recurrence and/or disease-free survival, exon 11 deletion and hemizygous mutation status were both independent factors highly predictive for poor survival. Conclusion  The authors conclude that KIT exon 11 deletions and somatic loss of the wild-type KIT identified patients with poor prognosis. Age, clinical stage, tumor size, and mitotic count were standard clinicopathologic features that significantly influenced the prognosis. Mutation type of the mitogen receptor c-kit has a potential for predicting the course of the disease and might contribute to management individualization of GIST patients. Ying-Yong Hou and Florian Grabellus contributed equally to this work.     

Predicting the Antitumor Effects of STI571 by Analysis of c-kit Gene Mutations in Gastrointestinal Stromal Tumors of the Stomach: Report of a Case

We report a case of a large gastrointestinal stromal tumor (GIST), greater than 5 cm in diameter, in the stomach. Microscopically, high levels of mitosis were observed, indicative of a high-grade malignancy. We analyzed the c-kit gene mutations by a replication competent retrovirus assay and DNA sequencing, which revealed a c-kit mutation in exon 11. Liver metastases were detected 7 months after surgery. Patients with an exon 11 mutation of the c-kit gene are reported to have a high response to STI571 (imatinib mesylate, Glivec). Accordingly, a 1-month course of STI571 treatment clearly changed the characterization of the metastatic tumors radiographically. Thus, it may be important to analyze c-kit gene mutations in patients presenting with GISTs to predict the effectiveness of STI571 in suppressing GISTs, especially tumors thought to have malignant potential.     

胃肠道间质瘤伊马替尼术前治疗进展

目的 探讨伊马替尼术前治疗胃肠道间质瘤（gastrointestinal stromal tumor,GIST）的作用。 方法 采用文献复习的方法,对研究伊马替尼术前治疗GIST的文献加以综述。 结果 伊马替尼术前治疗是进展期GIST的有效治疗手段,能显著提高患者的手术切除率,延长总体生存时间。 结论 术前伊马替尼治疗转移性或局部进展期GIST疗效较好,应参考GIST基因分型结果个体化术前给药,值得进一步深入临床研究。     

Secondary c-kit Mutation in a Recurrent Gastrointestinal Stromal Tumor Under Long-Term Treatment with Imatinib Mesylate: Report of a Case

Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the c-kit receptor gene, which are targets for imatinib mesylate. However, imatinib resistance is an increasing clinical problem. We herein present such a case with a recurrent GIST, in association with the development of a secondary mutation in the c-kit gene. A 67-year-old man, who had a GIST of the stomach with multiple liver metastases, underwent a partial gastrectomy, distal pancreatectomy, and partial hepatectomy. After surgery, he was treated with imatinib. However, during the approximately 4-year treatment period, a recurrence of the GIST in the liver was detected, for which a partial hepatectomy was again performed. The primary GIST constitutively had a deletion mutation in exon 11. In addition, the recurrent hepatic tumor developed a secondary point mutation (Val654Ala) in exon 13, which may be responsible for the imatinib resistance.     

Single-Incision Sleeve Gastrectomy for Successful Treatment of a Gastrointestinal Stromal Tumor

Background:

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that are located specifically in the gastrointestinal tract, with up to 60% of occurrences in the stomach, 30% in the small intestine, and 10% in the esophagus, colon, and rectum. The annual incidence of GISTs is about 15 cases per million, which in the United States equals 5000 cases per year. In most cases, these tumors are asymptomatic and are found incidentally on computed tomography scan or by endoscopy. Preoperative evaluation is based on location, size, and anatomic features and helps to confirm the diagnosis of the GIST and assess outcomes. Surgical intervention is the gold standard for treatment of nonmetastatic GISTs.

Case Presentation:

We report the case of an 80-year-old man with a gastric mass on the posterior surface of the greater curvature of the stomach at the junction of the gastric antrum and the pylorus, found incidentally on a computed tomography scan. The patient underwent a diagnostic laparoscopy and a single-incision laparoscopic sleeve gastrectomy. After histologic evaluation, the resected lesion was determined to be a gastrointestinal stromal tumor.

Conclusion:

A single-incision laparoscopic sleeve gastrectomy for the resection of GISTs is a feasible and appropriate method if the lesion is a safe distance from the pylorus and the gastroesophageal junction for gross negative margins to be obtained. Its advantages include decreased pain and a shorter hospital stay compared with other methods.     

胃肠道间质瘤的诊治现状与进展

目的总结胃肠道间质瘤（GIST）的发病机制及流行病学特点,探讨其诊断及治疗并分析其预后。方法复习与GIST的发病机制、流行病学、诊断、治疗及预后方面有关的文献并对其进行综述。结果 GIST为非上皮源性肿瘤,起源于Cajal间叶细胞,是消化道最常见的间叶性肿瘤,约占消化道肿瘤的1%～3%,中位发病年龄为40～60岁,胃为最好发部位。目前认为,GIST的发病机制与原癌基因c-kit或血小板源性生长因子受体α（PDGFRα）基因突变有密切关系,但PDGFRα和c-kit基因突变不会同时出现在同一患者中。GIST的临床表现缺乏特异性,临床诊断主要依靠内镜及影像学技术,最终确诊依靠病理学检查。目前对GIST的治疗以手术与分子靶向药物治疗为主,其预后与肿瘤危险度分级及治疗干预密切相关。结论 GIST是具有恶性潜能的肿瘤,其危险度分级是指导临床治疗及预后评估的重要指标,GIST的预防、诊断、治疗及复发的预防有待进一步研究。     

肛门直肠间质瘤治疗体会(附12例报告)

目的探讨肛门直肠间质瘤的诊断和治疗。方法回顾性分析我院2008年至2013年收治的12例间质瘤患者的临床资料。结果 12例其中男5例,女7例。年龄40~84岁,平均53.33±13.44岁。肿瘤大小在1~5cm之间,平均2.0±1.37cm。其中高危3(25%)例,中危4(33.3%)例,极低危5(41.6%)例。病理核分裂象5/50HP为7例。CD117阳性10(91.67%)例,CD34阳性8(75%)例。目前患者均存活,随访时间27.75±15.21个月,复发4(33.33%)例。结论对肛门直肠间质瘤应进行规范化的诊断和治疗,尽量减少复发。     

胃肠道类癌

为探讨胃肠道类癌的临床诊断、治疗和病理学特点。对６２例胃肠道类癌进行了系统的病理组织学观察及总结，其中４６例行局部切除，１６例做了根治性手术，随访１～１０年，死亡４例。作者认为：病理学诊断是类癌最后确诊的主要方法，手术切除的范围取决于原发肿瘤的大小、部位、浸润程度、淋巴结受累及有无肝转移情况     

胃肠道间质瘤临床诊治分析(附48例报告)

目的探讨胃肠道间质瘤（GIST）的诊断与治疗。方法对我院1999年1月至2004年12月收治的48例GIST患者的病理特点及外科治疗进行回顾性分析。结果本组GIST发生部位：胃29例（60．4％），小肠11例（22．9％），结肠3例（6．3％），直肠4例（8．3％），肛管1例（2．1％）。主要临床表现为消化道出血（52．1％）和腹部肿块（35．4％），免疫组化表型CD117阳性率为83．3％（40／48），CD34阳性率为77．1％（37／48），SMA阳性率为27．1％（13／48），S-100阳性率为22．9％（11／48）。48例均行手术切除。全组术后均未行放、化疗，随访12-60个月，平均35个月，随访率为100％。良性及交界性患者均无复发；13例恶性者中6例复发，其中5例死亡。结论GIST在中老年人中好发，部位以胃及小肠最多见，以消化道出血、腹部肿块表现为主。肿瘤的大小是GIST良、恶性的重要临床指标。GIST的诊断有赖于病理形态学检查与免疫组化的结合。完整的局部手术切除是最有效的治疗手段。