胃肠道间质瘤与胃肠道自主神经瘤

以往，临床、影像及病理工作者对消化道平滑肌肿瘤的存在深信不疑，并且认为平滑肌肿瘤是消化道最常见的间叶源性肿瘤。当前，人们已将消化道间叶源性肿瘤(gastroin-testinal mesenchymal tumor，GIMT)以平滑肌肿瘤为主的观点逐渐转变到以胃肠道间质瘤(gastrointestinal stromal tumor，GIST)为主的观点上来，大量文献报道了当前认识的GIST临床病理、免疫表型及分子生物学特点.     

不同部位胃肠道间质瘤免疫组化表达的研究

目的　探讨不同部位胃肠道间质瘤(gastrointestinalstromaltumors,GIST)免疫组化表达谱的一般规律及变异。方法　用CD117、CD34、α-SMA、S 100蛋白等抗体对205例GIST进行免疫组化染色。结果　CD117在原发性GIST中总阳性率为96 6%,阳性表达与部位无关,CD34在消化道不同部位GIST阳性率分别为食管(3 /3)、胃88 5% (108 /122)、小肠42 .9% (21 /49)、结肠66 7% (2 /3)、直肠100% (28 /28),小肠GISTCD34阳性率最低,与其它部位比较差异有显著性(χ2 =52 50,P<0 001)。α-SMA、MSA在不同部位GIST中的表达呈现与CD34相反的规律,小肠阳性率最高,分别为40. 8% ( 20 /49 ) (χ2 =11 47,P<0 01)和26 5% (13 /49),GIST中desmin偶尔局灶阳性(2 2% ),S 100蛋白、PGP9 5总阳性率为17. 0%和12. 5%,均以小肠阳性率较高,分别为24. 5%和22. 4%。结论　CD34、αSMA、MSA以及S 100蛋白、PGP9 5在GIST中的表达与GIST的部位有关,了解此规律对避免将表达αSMA、MSA的小肠GIST诊断为平滑肌肿瘤具有重要参考价值。此组抗原谱在GIST的变化规律可能与消化道不同部位卡哈尔间质细胞(interstitialcellsofCajal,ICC)的内在特征有关。     

胃肠道间质瘤的研究进展

胃肠道间质瘤是消化道内的一种间叶性肿瘤,近年来才逐渐被大家所认识。免疫组织化学研究发现,绝大多数胃肠道间质瘤特征性表达CD117。随着分子生物学技术的发展,发现肿瘤细胞的c-k it基因或血小板衍生生长因子受体α基因存在突变。外科手术是惟一有治愈可能的治疗方法,但药物伊马替尼可以治疗有些不能手术的肿瘤或已经发生转移的肿瘤。但此药物与多种因素有关,包括肿瘤细胞的基因突变类型。     

胃肠道小间质瘤的研究进展

胃肠道间质瘤(gastrointestinalstromaltumor,GIST)是胃肠道最常见的间叶性肿瘤,约占胃肠道间叶性肿瘤80%.根据肿瘤大小、核分裂像计数以及肿瘤发生的部位将胃肠道间质瘤分为极低、低、中等和高度危险性.体积<2cm的间质瘤,称为小间质瘤.不同危险度的间质瘤其临床表现、生物学行为、遗传学表现和预后明显不同,小间质瘤的临床表现及预后明显好于大间质瘤.C-Kit基因突变是胃肠道间质瘤发生发展的驱动基因,因大小间质瘤C-Kit基因突变相似,导致对C-Kit基因突变在胃肠道间质瘤中的作用引起争议.本文综述小间质瘤的流行病学、临床病理表现、分子遗传学、治疗与预后的研究进展.     

胃肠道间质瘤临床病理研究进展

传统上,胃肠道原发性间叶源性梭形细胞肿瘤几乎都归为平滑肌肿瘤,包括平滑肌瘤与平滑肌肉瘤及它们的各种亚型,但新近研究表明,大多数胃肠道间叶源性肿瘤既不同于典型的平滑肌瘤,也不同于雪旺瘤,而是一组具有不同特征的肿瘤,称为胃肠道间质瘤(ｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌｓｔｒｏｍａｌｔｕｍｏｕｒｓ,ＧＩＳＴｓ)。研究发现较特异和最具实用意义的诊断标准是免疫组织化学检测ｃｋｉｔ基因产物(ＣＤ117)和ＣＤ34的表达〔1,2〕。由于ＧＩＳＴ涵盖了绝大部分胃肠道间叶源性肿瘤,而真正的胃肠道平滑肌瘤及雪旺瘤很少见,因此,作者综合近年…     

对胃肠道间质瘤的再认识

胃肠道间质瘤 (gastrointestinalstromaltumor,GIST)是消化道最常见的间叶源性肿瘤 ,长期以来一直被诊断为消化道平滑肌 (肉 )瘤或 (恶性)神经鞘膜瘤。 1 983年 ,Mazur和Clark运用电镜和免疫组织化学重新评估胃间叶源性肿瘤的组织发生 ,发现除个别病例具有明确的平滑肌和神经鞘膜免疫表型和超微结构特征外 ,大部分肿瘤无明确肌性或神经分化特征 ,类似未分化的幼稚间充质细胞 ,从而提出GIST的概念 ,作为在当时情况下难以明确这类肿瘤分化方向的临时替代名称。此后 ,各国学者对GIST进行了深入研究 ,但直至近年发现该肿瘤存在c kit基因的…     

野生型胃肠道间质瘤研究进展

胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是胃肠道中常见的间叶性肿瘤。经研究证实,大多数肿瘤存在KIT/PDGFRA基因的激活突变。其中,约85%的儿童GIST和10%～15%的成人GIST无KIT/PDGFRA基因突变,其被定义为野生型GIST。该文现对野生型GIST常见突变类型的分子特征、发病机制和治疗进行综述。     

胃肠道间质瘤88例诊治分析

目的 探讨胃肠道间质瘤的诊断及治疗.方法 回顾分析我院2002年2月～2010年6月经手术证实的88例胃肠道间质瘤的临床资料.结果 肿瘤发生于胃44例,小肠20例,肠系膜9例,结直肠6例,十二指肠3例,肝脏3例,盆腔2例,食管1例.完整切除80例,因肿瘤广泛转移行局部切除或活检8例.无手术死亡病例,62例获随访,13例术后复发.结论 外科手术是治疗GIST的首要措施,伊马替尼的靶向治疗可改变复发或转移病人的预后.     

胃肠道间质瘤恶性指标的研究

目的 探讨一组临床病理指标在预测恶性胃肠道间质瘤(GIST)中的价值.方法 回顾性研究840例GIST,假设肉眼播散[包括肝转移和(或)腹腔播散]、显微镜下播散(包括淋巴结转移、血管浸润、脂肪浸润、神经浸润和黏膜浸润)以及肿瘤复发为恶性组,剩余为生物学行为不明组,根据此初步分组后进行多因素分析.结果 多因素分析发现以下形态学指标与恶性组密切相关:核分裂象≥10个/50 HPF、肌层浸润、肿瘤性坏死、围绕血管呈簇状排列以及细胞明显异型(均P<0.01).由此获得了2项肉眼播散、5项镜下播散和5项组织形态学指标.485例具有其中任意一项指标者归入恶性组,其余355例为非恶性组.随访资料提示非恶性组患者5年无瘤生存率(DFS)及5年总生存率(OS)分别为99.3%和100%,而恶性组患者5年DFS及5年OS分别为43.9%和59.7%,恶性组与非恶性组5年DFS与5年OS差异有统计学意义(均为P<0.01).结论 此组12项临床及形态学指标能有效地将恶性GIST从非恶性GIST中区分开来,可用于区分GIST的性质.     

胃肠道间质瘤的组织发生及命名

胃肠道间质瘤(ｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌｓｔｒｏｍａｌｔｕｍｏｒｓ,ＧＩＳＴ)被认为是一类既不同于典型平滑肌瘤亦不同于雪旺瘤的胃肠道最常见的间叶源性肿瘤(ｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌｍｅｓｅｎｃｈｙｍａｌｔｕｍｏｒｓ),近年来,在病理诊断中已频繁使用ＧＩＳＴ这一名称。但在ＧＩＳＴ的起源、分化、命名等方面一直存有争议,各种不同的名称如上皮样或奇异型平滑肌瘤、平滑肌母细胞瘤或上皮样平滑肌肉瘤以及胃肠道自主神经瘤(ｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌａｕｔｏｎｏｍｉｃｎｅｒｖｅｔｕｍｏｒｓ)等都曾用来描述…     

PKCtheta expression in gastrointestinal stromal tumor.

Gastrointestinal stromal tumor is characterized by a gain of function mutation of KIT gene and the expression of c-kit protein, but in 5% of cases, c-kit expression is negative although histological findings of gastrointestinal stromal tumor are most suspicious. The existence of c-kit-negative gastrointestinal stromal tumors points to the need of additional markers for making the diagnosis. In this study, we studied the expression of PKCtheta and correlated their expression with other immunohistochemical profiles of gastrointestinal stromal tumors and evaluated their usability as a diagnostic marker. For this purpose, 220 gastrointestinal stromal tumors were immunohistochemically stained for PKCtheta, c-kit, CD34, alpha-smooth muscle actin and S-100 protein. Additionally, genetic studies of KIT and PDGFRA genes were performed using c-kit-negative or PKCtheta-negative cases. All the 220 masses were either PKCtheta-positive or c-kit-positive. PKCtheta was positive in 212 (96%) cases and c-kit was positive in 216 (98%) cases in the cytoplasm of tumor cells with a diffuse staining pattern. Out of 212 PKCtheta-positive GISTs, 208 (98%) cases were c-kit-positive, 174 (82%) cases were CD34-positive, 62 (29%) cases were SMA-positive and S-100 protein was positive in 54 cases (26%). Genetic analyses on eight PKCtheta-negative cases showed exon 11 mutations of KIT gene in four cases. Two PKCtheta-positive and c-kit-negative GISTs showed mutations of PDGFRA gene. Our study shows that PKCtheta is a useful marker and it may play a role in the development of gastrointestinal stromal tumors. Together with c-kit, PKCtheta immunostaining can be used as an important diagnostic tool in the pathologic diagnosis of gastrointestinal stromal tumors with its high specificity and sensitivity.     

HER-2 status in gastrointestinal stromal tumor

Human epidermal growth factor receptor–2 (HER-2) encodes for the transmembrane glycoprotein HER-2 that is involved in activation of intracellular signal transduction pathways that control cell growth and differentiation. HER-2 is overexpressed in approximately 20% of patients with breast cancer and has been associated with poorer prognosis. Since 1998, the anti–HER-2 antibody trastuzumab has been used for the treatment of patients with HER-2–positive breast cancers. However, little information is available about the relationship between HER-2 and gastrointestinal stromal tumors. This study's purpose was to determine the HER-2 status in gastrointestinal stromal tumors. We found that all 477 cases included in this study were negative (score 0) by immunohistochemistry using HercepTest, and no HER-2 gene amplification was detected in 71 cases submitted to fluorescence in situ hybridization. These results show that HER-2 may not have any role in gastrointestinal stromal tumor pathogenesis and that the neoplasm may not be suitable for treatment with trastuzumab.     

RNAi沉默 N-cadherin 表达对 EC9706细胞裸鼠移植瘤生长的影响

目的: 探讨RNAi沉默 N-cadherin 表达对人食管鳞状细胞癌EC9706细胞体内生物学行为的影响。方法: 通过逆转录病毒介导的RNAi技术将 N-cadherin 基因的RNA干扰载体pMSCVneo/N-cadherin质粒及对照质粒pEGFP-MSCVneo质粒分别转染至人食管癌细胞系EC9706,运用G418进行抗性克隆的筛选和扩增,进而得到稳定转染的人食管癌细胞系EC9706(分别命名为干扰载体组和空载体组),将正常对照组、空载体组和干扰载体组EC9706细胞通过皮下注射的方式接种于裸鼠背部肩胛区,比较各组裸鼠成瘤期、成瘤大小、瘤体终重量及终体积等情况。运用免疫组织化学方法和Western blotting方法检测3组裸鼠移植瘤组织中E-cadherin、N-cadherin和MMP-9蛋白的表达情况。TUNEL法检测3组裸鼠移植瘤组织中细胞的凋亡水平。结果: (1)与正常对照组和空载体组相比较,干扰载体组裸鼠移植瘤的生长速率、成瘤大小、瘤体终重量和终体积明显降低(P<0.05)。(2)与正常对照组和空载体组相比,干扰载体组裸鼠移植瘤组织中N-cadherin和MMP-9的蛋白表达均下调(P<0.05),而E-cadherin的蛋白表达则无明显变化(P>0.05)。(3)与正常对照组(51.55±4.68)和空载体组(54.17±5.26)相比,干扰载体组(106.81±6.47)裸鼠移植瘤组织中凋亡的阳性细胞数明显增加(P<0.05)。结论: RNAi沉默 N-cadherin 表达可明显抑制EC9706细胞裸鼠体内移植瘤的生长,其作用机制可能是通过下调MMP-9的表达,降低细胞对细胞外基质的降解能力,进而降低EC9706细胞的体内侵袭力。RNAi沉默 N-cadherin 表达具有体内抑制食管鳞状细胞癌细胞生长的作用。N-cadherin可望成为抗食管鳞状细胞癌治疗的潜在分子靶点。     

Malignant gastrointestinal stromal tumor of the gallbladder

Gastrointestinal stromal tumors (GISTs) of the gallbladder are representative of an extremely rare group of tumors. We have encountered a patient with a malignant GIST of the gallbladder and presented it with a review of some articles. A 72-yr-old woman initially presented with right upper quadrant abdominal pain, fever and chills. Emergency cholecystectomy was performed under the impression of gallbladder empyema. Liver metastasis was found at 7 months postoperatively and the patient expired 9 months after the surgery. At the time of cholecystectomy, the gallbladder showed a necrotic serosal surface with an irregular thickened wall. A mass, 6 cm in length and 3 cm in width, encircled the whole wall of the neck and upper body of the gallbladder. Microscopic findings revealed frequent mitotic figures (more than 20/50 HPF) and tumor necrosis. Hyperchromatic, pleomorphic and spindle shaped neoplastic cells that were arranged in a pattern of short fascicles infiltrated the entire layer of the gallbladder. The tumor cells were immunoreactive for CD117 antigen (c-kit protein) and vimentin. They were negative for desmin, smooth muscle actin and S-100 protein. Mutations of the c-kit proto-oncogene were not found in this case. These findings were sufficient to provide enough clinical, histopathological and immunohistochemical evidence in diagnosing our case as a malignant GIST.     

Immunohistochemical comparison of gastrointestinal stromal tumor and solitary fibrous tumor

CONTEXT: The differential diagnosis of gastrointestinal stromal tumors (GIST) and solitary fibrous tumors (SFT) may be a diagnostic challenging because of overlapping clinicopathologic features. Many studies have shown consistent immunoreactivity for CD117 (c-Kit) in GIST. However, only a few studies have evaluated CD117 expression in SFT, and these studies have used an antibody from Santa Cruz Biotechnology. In non-GIST lesions, reactivity with this antibody has been shown to differ from that with a CD117 antibody from Dako Corporation. The immunoreactivity of SFT with the Dako CD117 antibody has not been reported. Conversely, CD99 is a marker for SFT, and its expression in GIST has not been evaluated. OBJECTIVE: To study the immunohistochemical profiles of GIST and SFT to evaluate their diagnostic overlap. DESIGN: We studied the immunoreactivity of 27 unequivocal GIST and 19 unequivocal extra-abdominal SFT for CD117, CD34, CD99, alpha-smooth muscle actin, vimentin, CD31, S100 protein, and muscle-specific actin. All antibodies, including CD117, were from Dako Corporation. RESULTS: We found positive immunoreactivity for CD117 in 100% of GIST and none of SFT; for CD34 in 89% of GIST, and 100% of SFT; for CD99 in 89% of GIST and 100% of SFT; for alpha-smooth muscle actin in 48% of GIST and 31% of SFT; for vimentin in 89% of GIST and 90% of SFT; and for muscle-specific actin in 22% of GIST and none of SFT. None of the GIST or SFT showed immunoreactivity for CD31 and S100 protein. CONCLUSIONS: The major difference between GIST and SFT was strong CD117 immunoexpression in all GIST and an absence of this expression in all SFT. With the exception of muscle-specific actin, the prevalence of immunoreactivity for the markers studied did not differ substantially between these 2 tumors. We conclude that GIST and SFT show distinctly divergent immunoprofiles with respect to CD117 and muscle-specific actin.     

Prognostic significance of angiogenesis in gastrointestinal stromal tumor.

Angiogenesis is important in the growth and metastasis of various kinds of solid tumors. To investigate the potential role of angiogenesis in gastrointestinal stromal tumor (GIST), an immunohistochemical analysis was performed in 95 cases of GISTs for microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. MVD was evaluated with immunohistochemical staining for CD31. A high level of MVD was significantly correlated with overexpression of VEGF, tumor location (intestine>stomach), tumor size (> or =5 cm), tumor grade (high>intermediate>low grade) (P=<0.0001, 0.0422, 0.0006, 0.0359, respectively). Of the 70 GISTs analyzed, KIT exon 11 mutations were detected in 45 cases (64.3%) and KIT exon 9 mutations in two cases (2.9%). No mutations were found in KIT exons 13 and 17, and platelet-derived growth factor receptor-alpha exons 12 and 18. Interestingly, VEGF expression level was significantly higher in the non-KIT exon 11 mutant group than in the KIT exon 11 mutant group (P=0.0266). In univariate analysis, tumor grade (high grade), tumor size (> or =5 cm), mitotic count (> or =5/50 high-power fields), Ki-67 labeling index (> or =4.6%), MVD (> or =7.0/0.95 mm(2)) and VEGF expression (high) were significantly associated with a shorter period of disease-free survival (P=<0.0001, 0.0199, 0.0055 0.0027, 0.0028 and 0.0302, respectively). In multivariate analysis, tumor grade and MVD were identified as independent worse prognostic factors (P=0.0007, 0.0152, respectively). In conclusion, our results suggest that the evaluation of MVD and VEGF expression is useful for predicting the aggressive biologic behavior of GIST, and that angiogenesis associated with VEGF may play an important role, at least in part, in the progression of GIST.