胃肠道间质瘤19例临床病理分析

目的:探讨胃肠道间质瘤(gastrointestinalstromaltumors,GIST)的临床病理、免疫组化特征、鉴别诊断和治疗方法。方法:应用光镜观察形态特征,应用免疫组化SP法对胃肠道和胃肠外腹腔内原诊断为平滑肌瘤、平滑肌母细胞瘤和平滑肌肉瘤24例检测CD117、CD34、Vimentin、SMA和S100,获得19例GIST。结果:19例GIST占同期消化系统间叶肿瘤的79.2%(19/24)。抗体表达情况:CD11794.7%(18/19)、CD3463.2%(12/19)、Vimentin100%(19/19)、SMA15.8%(3/19)阳性和S100表达全部阴性。结论:GIST是消化道最常见的间叶性肿瘤。CD117、CD34、SMA和S100联合使用可协助鉴别诊断GIST。细胞密集、明显核异形、肿瘤性坏死以及核分裂数>5/50HP可作为恶性参考指标,手术切除是主要的治疗方式。     

胃肠道间质细胞瘤Nestin、PKC-θ和PTEN的表达及临床意义

目的探讨Nestin、PKC-θ和PTEN的表达在胃肠道间质瘤 （astrointestinal stromal tumors, GIST）组织中的诊断、鉴别诊断意义,及其与临床病理因素和危险度的关系。方法应用免疫组化S-P法,检测81例GIST组织中Nestin、PKC-θ和PTEN蛋白的表达情况,并对CD117、CD34、Vim、SMA、S-100重新进行标记,对这些病例进行危险度分级,并分析上述免疫组化指标与临床病理相关因素（性别、年龄、发生部位、组织学分型）和危险度的关系,并与平滑肌瘤和平滑肌肉瘤进行阴性对照研究。结果GIST组织中Nestin、PKC-θ和PTEN阳性表达率分别为86．4％（70／81）、88．9％（72／81）、88．9％（72／81）,Nestin和PKC-θ表达水平均与CD117（69．1％）有显著性差异（P〈0．05）,Nestin、PKC-θ在平滑肌瘤和平滑肌肉瘤表达均阴性,在26例CD117阴性表达中PKC-θ阳性表达,在6例PKC-θ阴性表达中CD117阳性表达。PKC-θ在良性和交界性GIST（x2=5．395,P=0．020）以及良性和恶性GIST中（χ^2=4．468,P=0．035）表达有显著性差异,PTEN的表达在良性和恶性GIST中有显著性差异（χ^2=6．255,P=0．012）。Nestin、PKC-θ和PTEN三种蛋白在不同性别、年龄、部位、瘤体大小、核分裂数和组织学类型之间表达水平均无显著性差异（P〉0．05）。结论Nestin和PKC-θ在GIST中高表达,作为胃肠道间质瘤的两种特异而敏感的新标志物,联合CD117对GIST的诊断及鉴别诊断有重要意义,PKC-θ和PTEN蛋白可以作为GIST分化程度的指标。     

胃肠道间质肿瘤

1胃肠道间质瘤（gastrointestinal stromal tumor,GIST）的发展历史 20世纪40年代,Stout等把间质瘤定义为胃肠道平滑肌瘤。20世纪60年代也有称为平滑肌肉瘤、成平滑肌瘤或奇异平滑肌瘤者;到60年代末期,随着电镜技术的发展,发现只有少数GIST细胞可见平滑肌特点,     

钙调蛋白结合蛋白在子宫平滑肌肿瘤诊断中的意义

目的　探讨高度敏感和特异的诊断子宫平滑肌肿瘤的指标。方法　选取子宫内膜间质肉瘤 2 6例 ,子宫普通型和富于细胞性平滑肌瘤各 2 5例 ,子宫平滑肌肉瘤 17例 ,正常子宫肌层和正常子宫内膜各 2 5例 ,采用免疫组化 S-P法检测各种组织中结蛋白、平滑肌肌动蛋白、雌激素受体以及重型钙调蛋白结合蛋白 (h-caldesmon)的表达。结果　正常的子宫肌层、子宫普通型平滑肌瘤、富于细胞性平滑肌瘤和子宫平滑肌肉瘤中重型钙调蛋白结合蛋白的表达分别为 10 0 .0 %、10 0 .0 %、96.0 %和 64.7% ,但正常子宫内膜和子宫内膜间质肉瘤细胞中均未见其表达。重型钙调蛋白结合蛋白诊断富于细胞性平滑肌瘤不仅敏感度高于结蛋白 ,而且特异度达 10 0 .0 %。结论　重型钙调蛋白结合蛋白可辅助正确鉴别子宫富于细胞性平滑肌瘤和子宫内膜间质肉瘤     

子宫富于细胞平滑肌瘤和子宫内膜间质肉瘤中肥大细胞的研究

目的　探讨肥大细胞在子宫富于细胞平滑肌瘤和子宫内膜间质肉瘤鉴别诊断中的意义及其作用机制。方法　选取 2 5例子宫富于细胞平滑肌瘤和 2 6例子宫内膜间质肉瘤标本 ,用免疫组化SP法检测两种组织中肥大细胞和增殖细胞核抗原PCNA的表达 ,同时检测富于细胞平滑肌瘤中雌激素受体和CD4 4v3的表达。结果　子宫富于细胞平滑肌瘤和子宫内膜间质肉瘤之间PCNA表达差异无显著性 (P >0 .0 5 ) ,而肥大细胞计数差异有显著性 (P <0 .0 1) ,用肥大细胞 <7/HPF诊断子宫内膜间质肉瘤的灵敏度为 10 0 % ,特异度为 92 .0 %。富于细胞平滑肌瘤中肥大细胞计数与CD4 4v3存在正相关 (rs=0 .5 89,P <0 .0 1) ,而肥大细胞数与PCNA和ER均无相关。结论　肥大细胞数可用来鉴别子宫富于细胞平滑肌瘤和子宫内膜间质肉瘤 ,但肥大细胞在子宫富于细胞平滑肌瘤中增加的机制及其作用尚待进一步研究。     

c-kit与p27蛋白在胃肠道间质瘤诊治中的临床意义

目的研究c-kit和p27蛋白在胃肠道间质瘤中的表达及其与间质瘤临床病理特征的关系,为GIST诊断、预后评估提供客观指标。方法收集54例手术切除的胃肠道间质瘤标本,同时取距瘤灶>5cm的正常组织,应用免疫组织化学S-P检测肿瘤组织及正常组织中c-kit和p27蛋白的表达。结果54例胃肠道间质瘤中,c-kit和p27蛋白阳性表达率分别为94.44%和59.26%。c-kit蛋白表达水平在GIST不同分化程度、有无复发及远处转移的差异无显著性意义(P>0.05),p27蛋白表达水平在GIST不同分化程度、有无局部复发间差异有显著性(P<0.01)。结论c-kit作为特异敏感的标志物,对GIST的诊断及鉴别诊断有重要意义,而检测p27蛋白可作为评估GIST恶性程度和判断预后的重要指标。     

胃肠道间质瘤的诊治

 引言胃肠道间质瘤 (gastrointestinalstromaltumor ,GIST)是一个随着临床病理技术发展而逐渐成熟的概念 ,是消化道最常见的间叶组织源性肿瘤。大量研究表明 ,以往诊断的胃肠道平滑肌肿瘤及神经鞘瘤大多数都属于GIST。目前比较公认的GIST的定义为 :GIST是胃肠道除外平滑肌肿瘤和神经鞘瘤及神经纤维瘤的、富于细胞且表达CD117的梭形、上皮样或多形性的间叶源性肿瘤 ,起源于向ICC(interstitialcellsofcajal)分化的未定形的间充质细胞。由于GIST确切的定义、组织来源、生物学行为、良恶性判断以及与胃肠道其他间叶性肿瘤的关系现存有不同意见 ,以致临床上诊断和治疗均较为困难。本文就GIST的目前诊治作一简要介绍。1　GIST的临床特征及生物学行为国外文献报道 ,GIST发病率约 1～ 2人 / 10万 ,占胃肠道肿瘤的 1%～ 4 % ,发病中位年龄在 5 5～ 6 5岁之间 ,4 0岁以前发病很少 ,儿童患此病更为罕见 ;男性稍多见或男、女性发病率相近 ;最常见于胃(6 0 %～ 70 % ) ,其次是小肠 (2 0 %～ 30 % ) ,结肠和直肠仅占 5...     

CD117在胃肠道间质瘤中表达的临床病理意义

目的：探讨CD117在胃肠道间质瘤（GIST）诊断及鉴别诊断中的应用价值。方法：应用EnVision法检测91例GIST及72例对照肿瘤CD117、CD34、α－SMA、S－100等的表达状况。结果：CD117几乎表达于所有良、恶性、不同部位的GIST，总阳性率为96.7%，平滑肌及神经源性肿瘤对照组CD117几乎均为阴性，CD34总阳性率72.5%，表达CD34的隆突性皮纤维肉瘤、上皮样肉瘤等CD117亦阴性。结论：CD117（克隆号sc168)作为GIST的辅助诊断指标具有极高的敏感性，与CD34合用，能辅助诊断绝大部分GIST，在胃肠道间叶源性肿瘤的鉴别诊断中有重要作用。     

CD117在胃肠道间质瘤中的表达及意义

目的探讨CD117在胃肠道间质瘤中的表达及其意义。方法应用免疫组织化学方法检测100例胃肠道间质瘤组织CD117的表达。结果 100例胃肠道间质瘤组织中,CD117阳性表达率为96.0%（96/100）,其中胃阳性率为96.9%（63/65）,小肠阳性率为96.4%（27/28）,腹膜后阳性率为85.7%（6/7）;良性间质瘤阳性率为96.4%（80/83）,交界性阳性率为91.7%（11/12）,恶性阳性率为100.0%（5/5）,CD117表达在不同部位间及不同生物学行为间差异均无统计学意义（P〉0.05）。结论 CD117是诊断胃肠道间质瘤特异性较高的抗体,在与胃肠道平滑肌肿瘤、雪旺氏肿瘤的鉴别诊断上也具有较高的价值;CD117的表达与间质瘤分布部位及良、恶性无关,不能作为分化程度的指标。     

胃肠道间质瘤中CD117 CD34和Ki-67的表达及其与危险度的关系

胃肠道间质瘤（gastrointestinal stromal tumor,GIST）是一类发生于胃肠道最常见的间叶性肿瘤，形态学上主要由棱形细胞和上皮样细胞组成，镜下很难与典型的平滑肌瘤、平滑肌肉瘤和神经鞘瘤相区别。近几年来随着免疫组化的开展和电镜研究的深入，人们对GIST有了新的认识。     

胃肠道间质瘤c-kit基因突变的研究

目的　探讨c kit基因在胃肠道间质瘤 (GIST)中的突变状况。方法　用PCR扩增和基因测序的方法 ,检测 5 2例GIST及 2 8例对照肿瘤c kit基因第 11号外显子序列 ,其中 30例GIST另检测了c kit基因第 9和第 13号外显子序列。结果　 2 5例恶性GIST中 ,14例有c kit基因 11号外显子突变 (5 6 .0 % ) ;2 7例良性及交界性GIST中 ,仅 2例有突变 (7.4 % )。良恶性GIST中 ,c kit基因突变的差异有显著性 (χ2 =14 .39,P <0 .0 1)。 5 2例GIST中 ,14例为杂合性突变 ,2例为纯合性突变。突变方式有点突变和片段的缺失或重复等 ,缺失和重复的片段为 3～ 4 8bp不等 ,碱基数是 3的倍数。原发及复发组织突变方式相同 ,突变病例瘤旁正常组织及伴发的腺癌无突变。对照肿瘤无c kit基因突变。GIST中c kit基因 11号外显子的突变位点多不固定 ,但有集中趋势 ,点突变和片段的缺失集中在5 5 0～ 5 70密码子 ,片段的重复集中在 5 70～ 5 85密码子。结论　 11号外显子的突变是恶性GIST的分子生物学机制之一 ,可作为辅助判断GIST良恶性的参考指标。c kit基因突变提示GIST是不同于消化道平滑肌瘤及神经鞘瘤的独立疾病。     

胃肠道间质瘤临床病理特点及诊治分析

目的 探讨胃肠道间质瘤(GIST)临床病理特点及诊治情况.方法 对31例GIST患者的临床资料进行回顾性分析.结果 全部患者均行手术治疗.31例GIST患者发生部位以胃(19例61.3%)和空肠(6例19.3%)为主.首发症状以腹痛、腹胀(20例64.5%)和消化道出血(12例38.7%)、腹部包块(8例25.8%)为主要表现.病理报告良性13例、潜在恶性2例、恶性16例.免疫组化CD117阳性28例(90.3%),CD34阳性26例(83.9%).结论 (1)GIST消化道症状无特异性,术前确诊率低,易造成误诊;(2)CD117和CD34阳性可以作为GIST的诊断标志;(3)治疗应以局部切除为主,恶性者应扩大切除范围.     

DNA计量图像分析诊断子宫平滑肌肿瘤的特异性及标准化检测

应用电子计算机辅助ＤＮＡ影像计量分析仪（ＣＭ１ＤＮＡＣｙｔｏｍｅｔｅｔ．ＨＵＮＤ，Ｗｅｔｚｌａｒ，Ｇｅｒｍａｎｙ）测量３０例人正常子宫平滑肌、内膜上皮、纤维及淋巴细胞核ＤＮＡＩＯＤ值，以确定子宫组织特异性正常二倍体参照细胞及其校正因子。测量８０例子宫平滑肌瘤细胞核ＤＮＡ含量，发现各ＤＮＡ计量结果与正常平滑肌近似，无１例出现干系ＤＮＡ非整倍体和＞９ｃＥＥ，有４例出现＞５ｃＥＥ。测量３２例生长活跃的子宫平滑肌瘤，１８例检出干系ＤＮＡ非整倍体，１例检出＞９ｃＥＥ，１１例检出＞５ｃＥＥ，测量２７例子宫平滑肌肉瘤，２２例出现干系ＤＮＡ非整倍体，５例出现＞９ｃＥＥ，１８例出现＞５ｃＥＥ。本文结果表明，用于系ＤＮＡ非整倍体和＞９ｃＥＥ作为指标诊断子宫平滑肌瘤的特异性均为１００％，诊断子宫平滑肌肉瘤的敏感性分别为８１％和１９％，对生长活跃的子宫平滑肌瘤恶性性质的预测具有重要意义。＞５ｃＥＥ这一指标阈值不适合用于对子宫平滑肌肿瘤良、恶性质的判断。     

101例胃肠道间质性肿瘤的免疫组织化学研究——组织发生学的探讨

本文通过101例胃肠道间质性肿瘤(GIST)的免疫组化研究,以探讨其组织发生学问题。所有病例均作Vimentin,HHF—35,Desmin和S—100蛋白的检测。在HHF—35和Desmin均阴性的29例,加染Neurofilament和GFAP。并选择了12例胃肠道外的平滑肌肿瘤对比。101例中,94％Vimentin阳性(良性94.6％,恶性93.8％),65.3％HHF—35阳性(良性67.6％,恶性64％),23.8％Desmin阳性(良性37.8％,恶性15.6％)和22.8％S—100蛋白阳性(良性27％,恶性20.9％)。在HHF—35和Desmin均阴性的29例Neurofilament和GFAP均阴性。支持大多数GIST是平滑肌来源的肿瘤。对比正常胃肠道壁和血管壁的平滑肌以及胃肠道外的平滑肌肿瘤,其对HHF—35和Desmin的反应明显较弱,可能是因瘤细胞分化处于早期阶段有关。文中分析了各部位和各组织学类型的GIST与其抗原表达的差异,发现与肿瘤分化有关,亦与部位有关,食道发生的常是分化很好的平滑肌肿瘤,胃、肠的分化差异较大,即使组织学上为典型的平滑肌瘤,其对HHF—35和Desmin的表达较食道的差。部分GIST对HHF—35反应阳性而Desmin阴性,尤以恶性者。提示HHF—35对发现分化较差的肌肉源性肿瘤较Desmin为敏感。     

42例胃肠道间质肿瘤的临床病理形态观察

目的：研究国人胃肠道间质肿瘤（gastrointe stinal stromal tumor，GIST）的临床病理形态特点。方法：应用光镜观察42例GIST的形态特征，用免疫组化S-P法检测CD117、CD34、SMA及S-100蛋白在GIST中的表达情况。结果：GIST的瘤细胞排列成交织束状、弥散片状、栅栏状或轮辐状，较为特征的是细胞团巢形成；胞质嗜酸性较经典的平滑肌瘤者为弱。瘤细胞为梭形或上皮样，或梭形与上皮样细胞混合存在。CD117和CD34的阳性率为92．9％（39／42）和76．2％（32／42）。结论：GIST是胃肠道最常见的间叶性肿瘤，有较为独特的组织学形态，CD117和CD34标记阳性是确诊GIST最有价值的诊断依据。     

Different Characteristics of Mitochondrial Microsatellite Instability Between Uterine Leiomyomas and Leiomyosarcomas

Uterine leiomyomas are benign tumors of the uterus that arise clonally from smooth muscle cells of the myometrium and are the most common reason for hysterectomies. The aim of this study was to evaluate mitochondrial microsatellite instability (mtMSI) in uterine leiomyomas and leiomyosarcomas to clarify the molecular pathogenetic distinction between these tumors. DNA was isolated from paired normal and tumoral tissues in 50 patients with uterine leiomyomas and 14 patients with leiomyosarcomas. mtMSI was analyzed by using eight microsatellite markers. Our result showed that mitochondrial microsatellite instability was not found in all uterine leiomyomas. However, 3 (21.4%) of 14 patients with leiomyosarcomas had mtMSI and the frequencies of mtMSI in these tumors were significantly different (p < 0.01). Distinctive characteristics of mitochondrial genetic instability in uterine leiomyomas and leiomyosarcomas suggested the potential of mtMSI as a marker for differential diagnosis between them.     

Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization

Uterine leiomyomas are the most prevalent tumor type in women of reproductive age and are the most common reason for hysterectomies. Although uterine leiomyomas are considered to be benign, they are a major public health concern for women. In contrast, leiomyosarcomas are rare but highly malignant uterine tumors. They may arise in uteri with preexisting leiomyomas and histologically sometimes resemble leiomyomas, thus causing controversy about whether leiomyosarcomas arise within leiomyomas. In this study, we used comparative genomic hybridization (CGH) to identify genetic alterations unique to each tumor type and alterations that are common between the two tumors. We analyzed 14 cases of uterine leiomyomas and eight cases of uterine leiomyosarcomas. Only two of the 14 leiomyomas exhibited genetic alterations, and those were restricted to gains on chromosomes 14 and 19 and losses on chromosomes 1 and 4. In addition, 68 leiomyomas were examined for loss of heterozygosity on chromosomes 1 and 4, and only three tumors exhibited any losses. In contrast, all eight leiomyosarcomas showed gains and losses of DNA by CGH, and in many cases multiple changes were observed. The most commonly observed genetic aberration, occurring in five tumors, was gains on both arms of chromosome 1, suggesting that this chromosome contains loci involved in the development of leiomyosarcoma. Our results do not provide evidence for the progression from benign leiomyoma to malignant leiomyosarcoma. Moreover, the large number of random chromosomal alterations in the leiomyosarcomas suggests that increased genetic instability plays a role in the formation of these tumors. Mol. Carcinog. 19:273–279, 1997. © 1997 Wiley-Liss, Inc. This article is a US Government work and, as such, is the public domain in the United States of America.     

Clinical Analysis of Diagnosis and Treatment of Gastrointestinal Stromal Tumors （Report of 96 Cases）

Objective To investigate the pathological diagnosis, surgical treatment and prognosis of gastrointestinal stromal tumors (GIST). Methods The clinicopathological data of 96 post-operative cases with GIST were analyzed retrospectively, and expression of immunohistochemical staining of CD117, CD34, SMA and S -100 was determined. Results Immunohistochemical positive staining showed: CD117, 79.1% (76/96); CD34, 58.3% (56/96); SMA, 35.4% (34/96); S-100, 9.3% (9/96). Twenty-three benign cases and 73 malignant cases were reported. The omentums were resected in 39 malignant cases. For the other 34 malignant cases the omentums were left intact. The recurrent and metastatic rates were 5.1% and 26.5%(P<0.05). The incisai section between the normal bowel and the tumor was >5cm in 46 cases, for the other 27 cases, the section was < 5cm. The recurrent and metastatic rates were 6.5% and 29.6%(P<0.05), respectively. The 5-year survival rates of benign and malignant GIST were 91.5% and 57.3%(P<0.05). Conclusion GIST were the most freuquent mesenchymal tumor seen in the gastrointestinal tract. The application of immunohistochemical markers CD117and CD34 are mutually beneficial for a final correct pathological diagnosis. The adaptation of a primary rational treatment, including the complete tumor resection and preventive omentectomy could reduce the recurrence of GIST.     

Helpful parameter for malignant potential of gastrointestinal stromal tumors (GIST)

BACKGROUND: Although a series of histopathological criteria have been suggested, the prediction of the malignant potential of gastrointestinal stromal tumors (GIST) is still difficult. The older literature called all gastrointestinal stromal tumors smooth muscle tumors or mixed GIST with true smooth muscle tumors. Reports on GIST including homogeneous cases were rare. METHODS: We examined 73 cases of GIST, which were immunohistochemically positive for c-kit and/or CD34, and mainly focused on the correlation between mitotic count and the other clinicopathological features to establish any helpful and reproducible parameters to indicate the malignant potential and to be used practically and objectively in the routine histopathological diagnosis of GIST. RESULTS: The results showed that there was a statistically significant difference in mitotic count between benign and malignant groups. Other proposed parameters, such as high cellularity, tumor size > or =5 cm, stomach and intestinal location, hemorrhage, necrosis, p53 expression and Ki-67 labeling index >10%, were frequently observed in tumors with mitotic figure. Three patients with one mitotic figure in 50HPF died from metastasis or recurrence of the tumors. CONCLUSIONS: Ki-67 index and cellularity should be used as predictors for the malignant potential of GIST. When other morphological features appear benign, mitotic count might also be a helpful practical factor in the prediction of the malignant potential of GIST.