Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Advancing gastrointestinal stromal tumor management: The role of imagomics features in precision risk assessment

BACKGROUND Gastrointestinal stromal tumors(GISTs)vary widely in prognosis,and traditional pathological assessments often lack precision in risk stratification.Advanced imaging techniques,especially magnetic resonance imaging(MRI),offer potential improvements.This study investigates how MRI imagomics can enhance risk assessment and support personalized treatment for GIST patients.AIM To assess the effectiveness of MRI imagomics in improving GIST risk stratification,addressing the limitations of traditional pathological assessments.METHODS Analyzed clinical and MRI data from 132 GIST patients,categorizing them by tumor specifics and dividing into risk groups.Employed dimension reduction for optimal imagomics feature selection from diffusion-weighted imaging(DWI),T1-weighted imaging(T1WI),and contrast enhanced T1WI with fat saturation(CET1WI)fat suppress(fs)sequences.RESULTS Age,lesion diameter,and mitotic figures significantly correlated with GIST risk,with DWI sequence features like sphericity and regional entropy showing high predictive accuracy.The combined T1WI and CE-T1WI fs model had the best predictive efficacy.In the test group,the DWI sequence model demonstrated an area under the curve(AUC)value of 0.960 with a sensitivity of 80.0%and a specificity of 100.0%.On the other hand,the combined performance of the T1WI and CE-T1WI fs models in the test group was the most robust,exhibiting an AUC value of 0.834,a sensitivity of 70.4%,and a specificity of 85.2%.CONCLUSION MRI imagomics,particularly DWI and combined T1WI/CE-T1WI fs models,significantly enhance GIST risk stratification,supporting precise preoperative patient assessment and personalized treatment plans.The clinical implications are profound,enabling more accurate surgical strategy formulation and optimized treatment selection,thereby improving patient outcomes.Future research should focus on multicenter studies to validate these findings,integrate advanced imaging technologies like PET/MRI,and incorporate genetic factors to achieve a more comprehensive risk assessment.

STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line,GIST-T1

AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.

Synchronic Duodenal Gastrointestinal Stromal Tumor and Neuroendocrine Tumor in Association with Neurofibromatosis Type 1: A Case Report

Introduction: The coexistence of synchronic duodenal gastrointestinal stromal tumor (GIST) and neuroendocrine tumor in a patient with neurofibromatosis type 1 (NF1) is extremely rare, and only eight cases were described in the literature. Clinical Case: This is a rare case of a 38-year-old female patient with NF1 who developed synchronic GIST and neuroendocrine tumor, which were both in the second portion of the duodenum. The first symptoms were abrupt digestive bleeding and anemia. Upper digestive endoscopy revealed two tumors, sizes 2.5 and 3.0 cm, in the second portion of duodenum, with biopsies identifying a GIST and a neuroendocrine tumor. Therapeutic decision was to proceed to surgical resection, and Whipple’s procedure was indicated. Surgical procedure was performed with good outcome. Currently the patient has excellent quality of life and maintains follow up for thirty months without recurrence. Discussion: Long-term disease-free survival and excellent quality of life are reported when these tumors are fully resected in this context. However, it is not always easy to access the gastrointestinal tract, especially the small intestine, and proceed to the histopathologic diagnosis of these tumors. Conclusion: It is important to be aware of the possibility of the coexistence of various tumors in the NF1 scenario for adequate screening, staging, and surgical treatment of these patients, as good prognosis can be achieved when such tumors are detected and treated properly.

DOG1 is useful for diagnosis of KIT-negative gastrointestinal stromal tumor of stomach

Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative staining.If the tumor is negative for KIT,but is positive for CD34,a histological diagnosis is possible.However,if the tumor is negative for KIT,CD34,S-100,and SMA,a definitive diagnosis is often challenging.Recently,Discovered on GIST-1(DOG1)has received considerable attention as a useful molecule for the diagnosis of GIST.DOG1,a membrane channel protein,is known to be overexpressed in GIST.Because the sensitivity and specificity of DOG1 are higher than those of KIT,positive staining for DOG1has been reported,even in KIT-negative GISTs.KITnegative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically.We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia.Our findings suggest that immunohistochemical staining for DOG1,in addition to gene analysis,is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.

Intraductal papillary bile duct adenocarcinoma and gastrointestinal stromal tumor in a case of neurofibromatosis type 1

We report our experience with a synchronous case of gastrointestinal stromal tumor(GIST) and intraductal papillary neoplasm of the bile duct(IPNB) in anelderly woman with neurofibromatosis type 1(NF-1). A 72-year-old woman presented with a 2-mo history of right upper abdominal pain unrelated to diet and indigestion. Fourteen years earlier, she had been diagnosed with NF-1, which manifested as café au lait spots and multiple nodules on the skin. Computed tomography(CT) revealed a multilocular low-density mass with septation, and mural nodules in the right hepatic lobe, as well as a 1.7-cm-sized well-demarcated enhancing mass in the third portion of the duodenum. The patient subsequently underwent right hepatectomy and duodenal wedge resection. We present here the first report of a case involving a synchronous IPNB and GIST in a patient with NF-1. Our findings demonstrate the possibility of various tumors in NF-1 patients and the importance of diagnosis at an early

Behavior of advanced gastrointestinal stromal tumor in a patient with von-Recklinghausen disease: Case report

Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen disease.In the current case,we report a 27-year-old woman with NF1,who presented with a lower abdominal mass,symptomatic anaemia,and significant weight loss.We employed multiple approaches to assess the tumor behavior,including computed tomography(CT)scan,surgical tumor resection,histological and immunohistochemical analysis and gene sequencing.Additionally,the patient was given Imatinib mesylate(Gleevec)as adjuvant therapy.CT scan delineated a large thick wall cavity lesion connecting to the small bowel segment.Resection of the tumor yielded a mass of 17 cm×13 cm with achievement of safety margins.The diagnosis was GIST,confirmed by immunohistochemical expression of CD117,CD34,and Bcl-2.Sequencing revealed no mutations in either KIT or platelet-derived growth factor receptor-alpha,genes which are mutated in over 85%of sporadic GIST cases.Further,there was no evidence of recurrence,metastasis or metachronous GIST for over three years in our patient.From our analyses,we believe selective genotyping is advisable for high risk patients to predict potential tumor behavior.

Neurofibromatosis type 1 with multiple gastrointestinal stromal tumors:A case report

BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 patients.In NF1-associated GIST,KIT and PDGFRA mutations are frequently absent and imatinib is ineffective.Surgical resection is first-line treatment.CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass.Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head,face,trunk,and limbs.Her abdomen was soft and nontender.No masses were palpated.Digital rectal examination was unremarkable.Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor.Laparoscopy was performed,which identified eight well-demarcated masses in the jejunum.All were resected and pathologically diagnosed as GISTs.The patient was discharged on day 7 after surgery without complications.No tumor recurrence was evident at the 6-mo follow-up.CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.

Clinicopathological and immunohistochemical analysis of gastrointestinal stromal tumor

AIM： To investigate the clinicopathological features of gastrointestinal stromal tumor （GIST） and to study the reference indexes for malignancy. METHODS： Fifty-two cases of primary GIST were distinguished from a group of gastrointestinal mesenchymal tumors using a panel of antibodies such as CD117 and CD34 by immunohistochemical SP method. Their biological behaviors were analyzed using the expression of p21WAF1 and Bax in 52 cases of GIST. RESULTS： Grossly, the tumor size was between 1.5 cm and 13 cm （mean： 5.5 cm）. Focal areas of hemorrhage, necrosis, or small cyst formation could be seen. Microscopically, the tumor was composed of spindle cells （20 cases）, epithelioid cells （20 cases） and mixed cells （12 cases）. Immunohistochemically, CDl17 and CD34 showed diffuse strong positive expressions, the positive rates were 98.1% and 92.3%. SMA, S-100, NSE, NF and MBP showed focal positive expressions, the positive rates were 48.1%, 28.8%, 25%, 21.2% and 42.3% respectively. Vimentins were all positive desmin and CgA were all negative. In normal adult stomach and intestine, the immunoreactive staining for CD117 and CD34 showed immunoreactive interstitial cells of Cajal in myenteric neuroplexus. Among the 52 cases of GIST, 27 were positive for p21WAF1 （51.9%）, 29 for Bax （55.8%）. The expression of p21WAF1 and Bax had no significent difference with the localization, size, histological subtype of GIST, but had a significent difference with the histological grade （P = 0.000, respectively）, p21WAF1 expression had a positive correlation to Bax expression （r = 0.461, P = 0.001, k = 0.459）. CONCLUSION： GIST has complicated arrangements and various cell types. Positivity of CD117 and CD34 is the most valuable factor in diagnosing GIST. Expression of p21WAF1 and Bax plays an important role in potential malignancy and malignancy rather than in benign GIST. p21WAF1 and Bax may be used as the markers in the assessment of GIST malignant potential.

Paraneoplastic focal segmental glomerulosclerosis associated with gastrointestinal stromal tumor with cutaneous metastasis: A case report

BACKGROUND Gastrointestinal stromal tumor(GIST)with cutaneous metastasis is very rare.As a result,cutaneous GISTs have not been well characterized.Focal segmental glomerulosclerosis(FSGS)is also a rare symptom among paraneoplastic nephritic syndromes(PNS).CASE SUMMARY In this case report,we describe a patient with cutaneous metastatic GIST accompanied by nephrotic syndrome occurring as a malignancy-associated PNS,for whom symptomatic treatment was ineffective,but clinical remission was achieved after surgery.Moreover,the patient has a missense mutation in NPHP4,which can explain the occurrences of GIST and FSGS in this patient and indicates that the association is not random.CONCLUSION This is the first reported case of a GIST with cutaneous metastasis accompanied by nephrotic syndrome manifesting as a PNS.

Histopathologic and Immunohistochemical Analysis of 66 Cases of Gastrointestinal Stromal Tumor

Background and Objective: To investigate the histopathological characteristics and immunohistochemistry of gastrointestinal stromal tumors (GIST). Immunohistochemistry (IHC) refers to the expression and meaning of CD117, DOG-1, CD34. Methods: Sixty-six gastrointestinal stromal tumor (GIST) samples with complete clinical data and definite clinicopathological diagnosis were collected from the Seventh Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022. Retrospective analysis was performed on the pathological data of 66 patients with GIST, and the histopathology and IHC were analyzed and summarized. Results: Among the 66 cases, 46, 14, 1, 5 were found in the stomach, small intestine, large intestine, and gastroenteral area. There were 45 cases (97%), 11 cases (79%), 1 case (100%), 5 cases (100%) in order of fusiform cell type. There were 1 case (3%), 2 cases (14%), 0 case, 0 case of upper dermatiform;Mixed type in 0 case, 1 case (7%), 0 case, 0 case;CD117 positive 66 cases (100%), DOG-1 positive 66 cases (100%), CD34 positive 61 cases (92%), CD117 and/or CD34 negative 5 cases (8%);CD34, CD117 and DOG-1 were negative simultaneously in 0 case. 19 cases (28%) were positive for SMA and 7 cases (11%) were positive for S-100. Conclusion: Fusiform cell type is the common type of GIST, followed by epithelioid type and mixed type, but the tumor sites are different, and the comparison cases are not completely the same. CD117, DOG-1 and CD34 are high surface in GIST, and the combination of SMA, S-100 and histomorphology can be used to diagnose most GIST.

X-染色体连锁凋亡抑制蛋白相关因子1通过自噬途径调控Caspase 1介导的胃肠道间质瘤细胞焦亡

目的:探究X-染色体连锁凋亡抑制蛋白相关因子1(XAF1)对人胃肠道间质瘤(GIST)细胞中半胱氨酸蛋白酶-1(Caspase 1)介导的细胞焦亡的影响及机制。方法:实时荧光定量PCR和Western blot检测人正常胃黏膜上皮细胞系(RGM-1)和GIST细胞系(GIST-T1、GIST-430、GIST-882)中XAF1的表达水平;采用脂质体介导转染法将pcDNA3.1-XAF1重组质粒染进GIST-882细胞,以构建高表达XAF1的GIST-882细胞。GIST-882细胞分为对照组、pcDNA3.1组(转染pcDNA3.1空载体质粒)、pcDNA3.1-XAF1组(转染pcDNA3.1-XAF1重组质粒)、pcDNA3.1-XAF1+Rap组(转染pcDNA3.1-XAF1重组质粒并给予自噬激活剂雷帕霉素处理),免疫荧光染色检测各组细胞内微管相关蛋白1轻链3(LC3)表达情况,Western blot检测各组细胞中LC3Ⅱ/LC3Ⅰ比值与Beclin1蛋白表达水平,ELISA法检测各组细胞上清中白细胞介素,IL-1β、IL-18含量,乳酸脱氢酶(LDH)释放实验检测各组细胞LDH释放率,Western blot检测各组细胞中Caspase-1及其活化形式cleaved-Caspase-1、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、消皮素D(GSDMD)蛋白表达水平。结果:与RGM-1细胞比较,GIST-T1、GIST-430、GIST-882细胞中XAF1 mRNA和蛋白相对表达量显著减少(P<0.05);细胞转染后,pcDNA3.1-XAF1组GIST-882细胞中XAF1 mRNA和蛋白相对表达量均显著高于pcDNA3.1组、对照组(P<0.05)。与对照组比较,pcDNA3.1-XAF1组GIST-882细胞内LC3荧光强度明显减弱,LC3Ⅱ/LC3Ⅰ比值、Beclin1蛋白相对表达量显著减少(P<0.05),细胞上清液IL-1β、IL-18含量及LDH释放率显著升高(P<0.05),Caspase-1、cleaved-Caspase-1、NLRP3、GSDMD蛋白相对表达量也显著增加(P<0.05);与pcDNA3.1-XAF1组比较,pcDNA3.1-XAF1+Rap组GIST-882细胞内LC3荧光强度明显增强,LC3Ⅱ/LC3Ⅰ比值、Beclin1蛋白相对表达量显著增加(P<0.05),同时,细胞上清液IL-1β、IL-18含量及LDH释放率显著下降(P<0.05),Caspase-1、cleaved-Caspase-1、NLRP3、GSDMD蛋白相对表达量也显著减少(P<0.05)。结论:XAF1在GIST细胞中表达下降,提高XAF1表达能通过抑制自噬从而促进Caspase 1介导的GIST细胞焦亡,发挥抗肿瘤作用。

细胞角蛋白19片段、蛋白激酶B和糖类抗原19-9水平联合超声内镜检查术对胃肠道间质瘤的鉴别价值

目的分析细胞角蛋白19片段(CYFRA21-1)、蛋白激酶B(PKB)和糖类抗原19-9(CA19-9)水平联合超声内镜检查术(EUS)对胃肠道间质瘤和非胃肠道间质瘤的鉴别价值。方法前瞻性纳入2020年1月-2023年7月该院收治的69例胃肠道间质瘤患者作为研究组,另择同期78例非胃肠道间质瘤患者(胃肠道平滑肌瘤25例,胃肠道神经鞘瘤53例)作为对照组。比较两组患者一般资料、EUS指标和肿瘤标志物,绘制受试者操作特征曲线(ROC curve),分析血清CYFRA21-1、PKB和CA19-9水平单独检测,以及联合EUS,对胃肠道间质瘤的诊断价值。结果与对照组比较,研究组灰度平均值、灰度标准偏差、血清CYFRA21-1、PKB和CA19-9水平更高(P<0.05)。不同性别和年龄的胃肠道间质瘤患者,灰度平均值、灰度标准偏差、血清CYFRA21-1、PKB和CA19-9水平比较,差异均无统计学意义(P>0.05)。与肿瘤直径≤5 cm、病理性核分裂象≤5个/50 HPF的胃肠道间质瘤患者比较,肿瘤直径>5 cm、病理性核分裂象>5个/50 HPF的胃肠道间质瘤患者,灰度平均值、灰度标准偏差、血清CYFRA21-1、PKB和CA19-9水平更高(P<0.05)。将胃肠道间质瘤纳入阳性,非胃肠道间质瘤纳入阴性,ROC curve显示,联合检测胃肠道间质瘤的诊断价值高于EUS、血清CYFRA21-1、PKB和CA19-9水平单独检测,曲线下面积(AUC)为0.936,敏感度为82.61%,特异度为91.03%。结论在胃肠道间质瘤中,CYFRA21-1、PKB、CA19-9水平、灰度平均值和灰度标准偏差升高,CYFRA21-1、PKB和CA19-9水平联合EUS在胃肠道间质瘤中诊断价值较高。

胃肠道间质瘤组织中Ki-67、CyclinD1、ICAM-1、Livin及MMP-9蛋白表达与危险度分级

目的:探讨胃肠道间质瘤组织中Ki-67、细胞周期素D1(CyclinD1)、细胞间黏附分子(ICAM-1)、凋亡抑制蛋白(Livin)及基质金属蛋白酶-9(MMP-9)蛋白表达与Fletcher分级的相关性。方法:应用免疫组化SP法检测67例胃肠道间质瘤存档蜡块标本中各蛋白的表达情况,单因素和多因素分析各蛋白表达与Fletcher分级的关系。结果:单因素分析结果显示,不同危险度分组中,Ki-67、CyclinD1、Livin及MMP-9蛋白表达的差异有统计学意义(P均<0.05)。有序Logistic回归多因素分析结果显示,CyclinD1和MMP-9对Fletcher分级影响显著,是Fletcher分级的独立影响因子,CyclinD1和MMP-9的优势比分别为3.51和3.29。结论:CyclinD1、MMP-9蛋白在胃肠道间质瘤组织中的表达与Fletcher分级具有明确的相关性,可作为判定恶性程度的参照因素。

胃肠道间质瘤124例DOG1、WISP-1表达与临床意义

目的探讨DOG1和WISP-1在胃肠道间质瘤(gastrointestinal stromal tumors,GIST)中诊断及预后的意义。方法收集川北医学院附属医院病理科124例有完整临床病理资料的GIST,应用免疫组化EnVision两步法检测了DOG1和WISP-1蛋白在124例GIST中的表达情况,并与非GIST进行对照研究;应用χ2检验及Spearmen检验对结果进行统计学分析。结果 124例GIST中DOG1的阳性表达率为96%(119/124),CD117的阳性变表达率为91.0%(111/124),两者在GIST中的表达水平差异无统计学意义(P>0.05);GIST与非GIST中DOG1的表达水平差异有统计学意义(P<0.001);本组病例中WISP-1阳性率为80.6%(100/124),其中极低风险性、低风险性、中风险性和高风险性的阳性表达率分别为44.4%(4/9)、66.7%(26/39)、86.9%(17/20)和95.0%(38/40),其阳性表达率与美国国立卫生研究院(NIH)风险分级呈正相关关系(P<0.001);GIST与非GIST中WISP-1的表达水平差异无统计学意义(P>0.05)。结论 DOG1是GIST中一个敏感又特异的标记物,与CD117联用能提高GIST的诊断准确率,临床上可将其作为鉴别消化道间叶源性肿瘤的一线抗体;WISP-1的表达可能和GIST恶性进程有关,有可能作为评估GIST生物学行为的指标。

胃肠道间质瘤组织中ESM-1和CD117的表达及意义

目的探讨内皮细胞特异性分子-1(endothelial cell-specific moelecule-1,ESM-1)和CD117的表达与胃肠道间质瘤(gas-trointestinal stromal tumor,GIST)临床病理特征的关系。方法采用免疫组化PV-9000法检测69例GIST组织中ESM-1和CD117的表达,分析与各病理参数的关系。结果69例GIST中ESM-1的高表达率91.3%(63/69),ESM-1高表达与GIST的生物学行为呈正相关(r=0.344,P<0.05),与肿瘤核分裂象及CD117表达存在相关;ESM-1表达与患者年龄、性别、肿瘤大小及分型无相关;CD117的阳性率为86.9%,随着GIST的生物学行为危险性及核分裂象的增加,CD117的表达率逐渐增加,相比差异有显著性。CD117表达与患者年龄、性别、肿瘤大小及分型无相关。结论ESM-1在GIST中存在广泛高表达,可能是GIST早期分子事件,并可能在GIST的发生发展中具有持续性。CD117和ESM-1的关系密切。

特异性生物标记物DOG1在胃肠间质瘤中的表达

目的探讨DOG1在胃肠间质瘤(GISTs)中的表达及其临床意义,并与CD117、CD34、SMA和S-100进行比较。方法收集68例GISTs病例,采用免疫组化SP法检测DOG1、CD117、CD34、SMA和S-100的表达,以瘤旁胃肠肌层组织和子宫平滑肌瘤、神经纤维瘤、纤维瘤作为对照。结果 68例GISTs中,DOG1、CD117、CD34阳性表达率分别为97.1%(66/68)、89.7%(61/68)、82.4%(56/68),DOG1和CD117的阳性率均显著高于CD34阳性率(P<0.05),且DOG1阳性率也显著高于CD117阳性率(P<0.05)。SMA和S-100在GISTs中均为(-)。结论 DOG1是胃肠间质瘤特异性生物标记,联合检测DOG1、CD117、CD34、SMA和S-100蛋白的表达对于确诊GISTs具有重要价值。

DOG1、CD117和PDGFRA在胃肠道间质瘤中的表达及相关性

目的:探讨DOG1、CD117和血小板衍生生长因子受体α(PDGFRA)在胃肠道间质瘤(GISTs)诊断中的意义,并分析与其GISTs临床病理因素和危险度的关系.方法:应用免疫组织化学Envision二步法检测63例GISTs及43例非GISTs间叶源性肿瘤患者中DOG1、CD117及PDGFRA的表达,并分析上述免疫组织化学指标与临床病理因素(性别、年龄、部位、肿瘤大小、核分裂象、组织学类型)和危险度的相关性.结果:GISTs中DOG1、CD117和PDG-FRA阳性表达率分别为84.13%(53/63)、90.48%(57/63)、52.38%(33/63),DOG1、CD117与PDGFRA相比,差异显著(均P<0.01),而其中CD117阴性的6例GISTs均表达DOG1阳性,5例表达PDGFRA阳性;非GISTs间叶源性肿瘤中DOG1、CD117及PDGFRA阳性表达率分别为11.63%、16.28%、6.98%.DOG1及PDGFRA的表达在不同性别、年龄、部位、肿瘤大小、核分裂象、组织学类型之间没有显著性差异,与危险度亦无相关性.但CD117的表达与部位及组织学类型有关(P=0.008,0.045),其他部位(肠系膜、腹腔、网膜)CD117表达率低于胃、小肠、结肠及直肠(50.00%vs94.74%,P=0.008).且梭型及上皮型中CD117高表达.结论:DOG1和CD117可以作为GISTs诊断的特异性标志物;对于KIT阴性的GISTs,DOG1检测的加入,将在病理学和临床上进一步完善诊断依据;DOG1、CD117和PDGFRA不能作为判断危险度的指标.

胃肠道间质瘤组织中Ki-67,细胞周期素D1和细胞间黏附分子-1的表达

目的：探讨胃肠道间质瘤（GISTs）组织中Ki-67、细胞周期素D1（Cyclin D1）和细胞间黏附分子-1（ICAM-1）的表达及其与肿瘤生物学行为的关系。方法：应用免疫组织化学sP法检测61例GISTs组织中Ki-67、Cyclin D1及ICAM-1的表达情况，分析上述指标与肿瘤临床病理学特征、危险度的关系。结果：GISTs组织中Ki-67标记指数（Ki-67 LI）〈1％、1％～5％和〉5％的例数分别为23例、17例和21例；Cyclin D1和ICAM-1阳性率为51％和59％。不同危险度组间Ki-67u和Cyclin D1的表达差异有统计学意义（P〈0．05）；不同危险度组间ICAM-1的表达差异无统计学意义；而有无复发转移组间ICAM-1表达差异有统计学意义（P〈0．05）。结论：Ki-67、Cyclin D1可作为判断GISTs恶性程度的参考因素．ICAM-1与GISTs的复发转移有关。

CD133、CD34、DOG-1在胃肠间质瘤中的表达及其意义

目的探讨与胃肠间质瘤诊断相关的生物标志物CD133、CD34、DOG-1的表达水平及其临床意义。方法收集胃肠间质瘤患者的病理切片150例作为研究对象,用免疫组化法对CD133、CD34、DOG-1的含量进行染色检测并分析。结果 CD133阳性表达率在年龄因素中的构成比差异具有统计学意义(P <0. 05),CD34阳性表达率在风险分级以及肿瘤直径因素中的构成比差异具有统计学意义(P <0. 05),而DOG-1阳性表达率在性别、肿瘤部位以及肿瘤浸润程度的构成比差异具有统计学意义(P <0. 05)。结论 CD133、CD34、DOG-1均高表达于胃肠间质瘤组织中,其中DOG-1的阳性表达率最高,并且三者可能存在协同刺激作用,共同促进了胃肠间质瘤的发生发展。