Gastrointestinal Stromal Tumor (GIST) with Chondroid-Myxoid-Chordoid Features Mimicking Extraskeletal Myxoid Chondrosarcoma

Epithelioid gastrointesinal tumors (GISTs) are less likely to have c-kit gene mutations (and express CD117) than spindle cell GISTs. CD117 negative/c-kit negative GISTs can have platelet-derived growth factor alpha (PDGFRα) gene mutations, overexpress PDGFRα protein and respond to imatinib mesylate. Many cases of CD117-negative/CD117-weakly positive, c-kit mutation negative and PDGFRα mutation positive myxoid epithelioid GISTs and one case of CD117-positive GIST with chondro-myxoid features mimicking chondrosarcoma have been reported. We report a case of myxoid epithelioid GIST with predominance of chondroid and chordoid areas resembling an extraskeletal myxoid chondrosarcoma that was strongly positive for CD117, PDGFRα and DOG1 (Discovered on GIST 1) by immunohistochemistry, but lacked c-kit and PDGFRα gene mutations. It is possible that CD117 is strongly positive if a myxoid epithelioid GIST has chondroid/chordoid appearance, but a larger study is needed to confirm this association. CD117 expression in GISTs is important, because GISTs showing CD117 positivity respond to imatinib. No comment can be made about the prognostic significance of chondroid/chordoid appearance in the GISTs.

Primary Extra-Gastrointestinal Stromal Tumor (GIST) arising from mesentery of small bowel and presenting as abdominal mass: A rare entity

Introduction: Majority of mesenchymal tumors of gastrointestinal tract are Gastrointestinal Stromal Tumor (GIST). It is, however, a rare tumor, accounting for less than 1% of primary gastrointestinal (GI) neoplasms. Though, these tumors are refractory to conventional chemotherapy or radiotherapy but show a good response to targeted adjuvant chemotherapy with tyrosine kinase inhibitors following surgical resection. Case Report: we report here a case of primary Extra-GIST tumor arising from mesentry of small bowel near duodeno-jejunal junction in a 69 years old male patient. The patient presented with a palpable mass in upper abdomen for past 15 days. On examination, a non-tender mobile lump of size around 17 × 10 cm, with bosselated surface and firm in consistency was palpable involving epigastric, left hypochondrium and umbilical region. Contrast enhanced computed tomography of abdomen revealed a heterogenous mesentric mass. On surgical intervention a mass was found involving mesentery near dudenojejunal junction without involvement of gastrointestinal tract. Complete surgical resection of the tumor was done and adjuvant chemotherapy with Imatinib mesylate was started as HPE revealing GIST with mitotic index of >10/50 HPF and 17 × 10 cm size placed the patient in high risk category. Patient was discharged on 12th of post-operative day with advice of regular follow-up. Conclusion: GIST occurrence is not restricted to bowel but can involve unusual sites also. The mainstay of treatment remains surgical resection with adequate margin. In cases where tumour has malignant potential (high mitotic figures on histopathology) adjuvent treatment with tyrosine kinase may prevent or delay relapse.

A Rare Cause of Pneumoperitoneum: Perforated Gastrointestinal Stromal Tumor (GIST)

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor and has a malignant potential. The clinical presentation with pneumoperitoneum and peritonitis is extremely rare. We report a case of a 40-year-old male presented with symptoms of acute abdomen. Radiological work-up confirmed pneumoperitoneum. Emergency laparatomy and complete resection were performed. The final diagnosis revealed perforated GIST originating from the jejunum. If an abdominal mass presents with pneumoperitoneum and peritonitis, jejunal GIST should be considered in diagnosis. A complete radical resection followed by postoperative adjuvant chemotheraphy with Imatinib is recommended.

Gastrointestinal Stromal Tumors (GISTs), Surgical Management and Clinical Outcome

Introduction: This study investigated the incidence, surgical management and outcome of Gastrointestinal Stromal Tumors (GIST) in Upper Egypt. Methods: A retrospective review of all GIST patients admitted a South Egypt Cancer Institute between Jan. 2010 and Dec. 2015 was conducted. Patients’ demographics, clinical presentation, tumor characteristics, radiological, pathological and immunohistochemical findings, surgical procedures, recurrence and mortality were recorded. Results: A total of 36 GIST patients were identified, stomach was the most common site (27.8%) followed by the small intestine (19.4%) and the large intestine (16.7%). The mean age at time of diagnosis as 52.8 ± 14.4 (ranged from 17 to 76 years). Of these 36 cases, 20 (55.6%) cases were males and 16 (44.4%) cases were females with a ratio of 1.2:1. About 22 cases (61.1%) presented with primary tumors, eight cases (22.2%) had primary tumors and metastases, three cases (8.35) presented with recurrent mass, whereas one case (2.2%) presented either with recurrent mass and metastases or metastases only. The majority of cases (22) had tumorsize >5 cm. Patients were stratified as high, intermediate, low and very low risk (50.6%, 30.6%, 11.1% and 2.8%, respectively). Almost all the cases were surgically managed and 75% were completely resectable. During follow up (average 26.5 months), 22 patients showed complete recovery, 7 had recurrent or metastatic disease and 2 died due to liver metastasis. Conclusion: The incidence of GIST in Upper Egypt is apparently low. Surgical resection is the preferred choice of treatment. The demographic data of GIST patients in South Egypt Cancer institute were similar to those published in the literature. Other prospective studies are required to assess the prognosis and the effect of treatment.

Management Colorectal Gastrointestinal Stromal Tumors (Gists) in Surabaya

Introduction: Colorectal gastrointestinal stromal tumors (GISTs) mesenchymal tumor is very uncommon. GISTs effect mostly on the stomach and small intestine and rarely occur in the colon, rectum and esophagus, that originating from precursors of the interstitial cells that originate of Cajal. The symptoms of gastrointestinal stromal tumor depend on the site and size of the tumor, and may include abdominal pain, gastrointestinal bleeding or signs of obstruction;small tumors may, however, be asymptomatic. Some of the patients with gastrointestinal stromal tumor have bloody stools, obstruction and abdominal pain as the commonest manifestation. Immunocytochemical staining for CD117 is helpful in confirming the diagnosis. Case presentation: We report 3 new cases of GISTs: two occurred at the rectal and the other at descending Colon. Two cases are over 50 years of age and, and all cases the chief complain of bowel obstruction, abdominal pain in two cases, and one case with anemia and urine retention. All the patients were operated and were permormed pathology examinatiom. All case ware positive result for immunocytochemical staining CD117. All cases we had presented had size more than 5 cm are considered as unfavorable prognostic factors to Fletcher criteria, all patients scheduled for chemotherapy with Glivec but just one patient continued to used Glivec. Post surgery follows up one patient post milles with urinary incontinence complaints found and that patients are trained to CIC (intermittent catheterization). Conclusion: Colorectal gastrointestinal stromal tumors are very rare and can present as mass abdomen. Resection and chemotherapy are the treatment of choice.

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.

Gastrointestinal stromal tumors and second primary malignancies before and after the introduction of imatinib mesylate

Gastrointestinal stromal tumor （GIST） is the most common mesenchymal malignancy of the gastrointestinal tract.GISTs may coexist with different types of cancer,either synchronous or metachronous （1）.Most GISTs develop in a sporadic fashion,but familial occurrence,such as neurofibromatosis and Carney-triad,has also been reported （2）.The overall frequency of second tumors in different series varied from 4.5% to 33%.The most frequent types of GIST-associated cancers were gastrointestinal carcinomas （47%）,lymphoma/leukemia （7%）,carcinomas of prostate （9%）,breast （7%）,kidney （6%）,lung （5%）,female genital tract （5%）,carcinoid tumors （3%）,soft tissue and bone sarcomas （3%）,malignant melanoma （2%） and seminoma （1%） （1,3-5）.

Repeat resection of liver metastases from gastrointestinal stromal tumor

A 44-year-old man, who was diagnosed with a gastrointestinal stromal tumor incidentally during emergency laparotomy for treatment of acute obstruction of small intestine at another hospital in 1999, was referred to our hospital due to a solitary metastasis in the liver in November 2002. A right segmentectomy (Segment 6, Couinaud's system) of liver was carried out. Half and one years later, a recurrent metastasis with involvement of the inferior vena cava was detected in posterior region of the liver. He underwent the third surgery in May 2004. Three another small metastases in greater omentum were found and removed. The tumor in posterior sector of the liver was en bloc resected with portion of involved inferior vena cava and diaphragm. The resected vena cava is repaired primarily through a lateral venorraphy.However, local recurrence was detected one year later, he recieved the fourth surgery in July 2005. He is now in Gleevec therapy. At present, he is in good health and free of recurrence.

Gastrointestinal stromal tumor of duodenum:a cause of upper gastrointestinal hemorrhage

Objective:The aim of the study was to report an anemia patient with melena for five years caused by duodenal gastrointestinal stromal tumor (GIST), who required surgical treatment. Methods: A 44-year old man present with anemia appearance was admitted to our center (Department of Hepatobiliary Surgery, Union Hospital, Huazhong University of Science and Technology, China) due to sustaining melena for five years. Endoscopy found no special mucosal abnormalities in the duodenal lumen. Computed Tomography showed a well-demarcated mass, 7.4 cm in diameter, located between the C loop of duodenum and pancreatic head. Pylorus-preserving pancreaticoduodenectomy and right hemicolectomy were performed when the patient's general conditions were improved. He recuperated successfully and was discharged on the 21st postoperative day. No complications happened during the period of hospital stay. Results: Histological and immunohistochemical study revealed a high risk invasive duodenal GIST which was positive for CD117, CD34, α-smooth muscle actin and negative for S-100. Conclusion: Duodenal GIST can be a source of upper gastrointestinal hemorrhage; surgical treatment is still a reasonable choice for the patients with invasive duodenal GIST.

<i>Ex vivo</i>evaluation of a prototype submucosal biopsy forceps for the diagnosis of gastric gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) account for approximately 2% of gastric cancers and can be challenging to diagnose due to the difficulty sampling tissue from these lesions. Current biopsy methods are inadequate for determining the mitotic index, a major prognostic factor of these tumors. We sought to evaluate the ability of a prototype submucosal biopsy forceps to make a histologic diagnosis and mitotic index determination in cases of resected gastric GISTs. After obtaining informed consent and surgical resection of three gastric GISTs, an investigational submucosal biopsy forceps and sheath was passed under direct visualization into the central portion of the tumors (in the ex vivo setting) and biopsies were obtained. The tumor was then processed for standard histology. A gastrointestinal pathologist, blinded to the mitotic index of the full specimen, evaluated the research biopsies. The results from the submucosal forceps biopsies were then compared with the standard histology results. n all 3 cases, the submucosal forceps biopsies confirmed the diagnosis of a GIST. In two out of three cases, the submucosal forceps biopsies accurately classified the risk for progressive disease (based on the mitotic index) when compared to standard histology. In one case, the research biopsy mitotic index would have resulted in an underestimation of tumor risk (biopsies categorized the lesion as “very low” rather than “moderate” risk).

A clinicopathologic and immunohistochemical study of gastrointestinal stromal tumors based on 122 cases

Objective:The aim of the study was to review the clinical records of 122 patients with gastrointestinal stromal tumors(GISTs) and analyze their clinicopathologic and immunohistochemical characteristics.Methods:The medic records of 122 patients with GISTs during the periods from January 2002 to May 2010 were reviewed.All tumors were confirmed by histological and immunohistochemical analyses.Results:The tumors occurred in 59 males and 63 females,ranging from 25 to 77 years.Of all cases,46 cases originated from stomach,42 from small intestine,17 from colon and rectum and 9 from retroperitoneal cavity and 4 cases from extra-gastrointestinal site.Liver was the most common organ that tumors metastases involved.Immunohistochemically,there were 114 tumors being positive for CD117 while 8 tumors negative for it.The frequencies of CD34 positive were higher in the stomach and rectum(89.1% and 86.7% respectively) than in the small intestine(64.3%,P < 0.05).Higher expression of SMA was in the tumors located in small intestine(54.8%) while the expressions of SMA in the gastric and rectal tumors were relatively low(21.7% and 20.0% respectively,P < 0.05).Conclusion:Gastrointestinal stromal tumors can occur in the gastrointestinal tract as well as in the extra-gastrointestinal sites.The frequencies of CD34 and SMA expression vary significantly with different locations.

COVID-19 in patients with gastrointestinal stromal tumors: Recommendations for management and vaccination

The coronavirus disease 2019(COVID-19)pandemic profoundly affected the management and treatment of patients with malignancies.Based on the progress reported in the literature,we reviewed the recommendations for treatment and vaccination in patients with gastrointestinal stromal tumor(GIST)during COVID-19.We focus on whether there is a risk and what could be the possible effects of vaccinating patients with GIST/cancer.Since the situation is quickly changing,and the health services have been severely disrupted,the diagnosis,treatment and recommendations for vaccination of these patients against COVID-19 are still not updated.The approval of vaccines in the pandemic gave hope that we would soon be able to return to a more normal life.However,the oncology community needs to adapt and provide the most effective treatment and care models for patients with rare cancer,such as GIST.Collecting data on the impact of vaccination in patients with GIST/cancer also will be beneficial in expanding knowledge about the future planning of treatment strategies and optimizing care in the event of a subsequent pandemic.

能谱CT影像组学及CT征象对GIST危险度分级探讨

目的本研究旨在探讨利用能谱CT影像学改变与CT征象联合建立的胃肠道间质瘤(GIST)危险度分级图模型,以评估其对临床精准治疗和GIST治疗的价值。方法我们纳入了本院术后病理确诊为GIST、同时有完整影像信息的135例患者进行研究,并收集73例外院确诊病例进行外部验证。根据2017年中国病理专家组的共识,将患者分为极低危、低危(入低危组)、中危和高危(入高危组)。我们将本院的135例病例作为训练组,外院的73例作为验证组,通过训练和验证独立的危险因素,进行特征筛选,利用能谱CT参数、CT表现预测模型和影像组学预测模型的独立危险因素进行多因素逻辑回归分析,并选取P<0.05的特征进行多因素逻辑回归建模,最终得出分级图。结果能谱CT参数,包括单能CT值、碘浓度、水浓度和有效原子数,计算能谱曲线的归一化碘浓度(NIC)和斜率k。评估其他的影像学变化,例如如肿瘤体积、生长模式、肿瘤坏死/溃疡、肿瘤供血或引流血管增生(EVFDM)、肿瘤边缘及临近组织浸润。在单因素分析中,70keV的结果更接近40keV~140keV单能量的平均值,图像噪声低、信噪比较高,低危组与高危组间在临近组织侵犯差异上有统计学意义(P<0.05)。多因素logistic回归分析显示,肿瘤大小、肿瘤坏死/溃疡、EVFDM、肿瘤轮廓及临近组织浸润(存在vs不存在)与较高的恶性潜力密切相关。将这些独立因素纳入列线图模型后,训练组和验证组的C指数分别为0.872(95%CI:0.753-0.863)和0.807(95%CI:0.697-0.893)。敏感度为0.865,特异性为0.915,诊断准确率为0.837。能谱CT影像组学联合CT特征列线图的AUC为0.927(训练组)和0.905(验证组),显示出了良好的预测。结论由能谱CT不同KeV影像学表现结合CT征象特征组成的胃肠道间质瘤列线图,包括大小、位置、肿瘤坏死/溃疡、EVFDM、肿瘤轮廓及临近组织浸润等,可以准确预测原发性胃肠道间质瘤的恶性潜力,对临床疗效评价和评估患者预后提供有效帮助。

Imatinib mesylate in clinically suspected gastric stromal tumors

Gastrointestinal stromal tumors （GISTs） occur most frequently in the stomach.Diagnosis of gastric GIST is not always clear before surgery.Flexible endoscopy may suggest the nature of the lesion （a bulky tumor with preserved mucosa）; however,biopsy is rarely diagnostic.Therefore,diagnostic medication with safe drugs may provide a feasible way under such conditions after an informed consent is obtained.Based on the excellent efficacy of imatinib mesylate （IM） in the treatment of GIST,we successfully applied it in the diagnostic medication of two patients with clinically suspected gastric stromal tumors.In conclusion,the diagnostic medication with IM can be an alternative option for patients with suspected GIST that can not be confirmed pathologically.

Expression and prognostic role of molecular markers in 99 KIT-positive gastric stromal tumors in Taiwan Residents

AIM： TO elucidate the prognostic role and relationship of three molecular markers such as tumor suppressor gene p53, proliferating cell nuclear antigen （PCNA） and Ki-67 in gastric stromal tumor. METHODS： A total of 108 surgically resected gastric smooth muscle tumor specimens were collected from January 1987 to December 1999. Immunohistochemical studies were performed on the paraffin sections of 99 of 108 CDl17-positive tumors with antibodies of p53, PCNA, and Ki-67. Immunoreactivity of three molecular markers was recorded by labeling index （LI, %） and was analyzed for clinicopathologic and survival correlation. RESULTS： Of the 99 cases, immunostaining revealed that 52 patients （52.5%） had p53, and 37 patients （37.3%） had Ki-67 immunoreactivity （defined as 〉10% of LI）. All patients （100%） had PCNA immunoreactivity ranging from 12% to 93% of LI, divided into high or low by median. Statistics revealed that LI of three markers positively correlate to each other （P〈0.01） and to microscopic tumor mitotic counts （P〈0.001）. By combination, patients with ≥2 markers （positive or high） in tumors had early tumor recurrence （P〈0.001） and unfavorable outcome （P〈0.001）. Univariate analysis indicated that patients with tumor size 〉5 cm （P=0.003）, tumor mitosis 〉5/50 HPF （P〈0.001）, p53 immunoreactivity （P=0.001）, Ki-67 immunoreactivity （P=0.026）, high PCNA LI （P=0.015） and male gender （P=0.036） were six predictors for early disease recurrence. Subsequent multivariate analysis revealed that mitotic counts, tumor size, and p53 immunoreactivity were three independent prognostic factors for both disease free and overall survival of patients. By combination of three independent prognostic factors for grouping, we found higher tumor recurrence rate （P〈0.001） and shorter survival （P〈0.001） existed in groups with increasing factors. CONCLUSION： We first provide the prognostic value and linkage of three molecular markers in GISTs. The combination of three factors （p53, tumor size, and tumor mitosis） provides a more powerful prediction of prognosis than any single factor does.

舒尼替尼治疗伊马替尼治疗失败或不能耐受GIST的毒副反应及其防治

目的探讨舒尼替尼(索坦)治疗甲磺酸伊马替尼治疗失败或不能耐受的胃肠间质瘤(GIST)患者的毒副反应情况及其防治措施。方法 2009年1月至2011年1月索坦治疗甲磺酸伊马替尼治疗失败或不能耐受的GIST患者41例,其中男性24例,女性17例,平均年龄55.5岁(29～82岁)。29例口服索坦50mg/日,5例口服索坦37.5mg/日,均为服用4周停药2周;另7例口服索坦37.5mg/日,连续服药。观察评估患者的毒副反应并给予相应的防治措施。结果索坦治疗过程中主要的不良反应分别为:白细胞减少75.6%(31/41)、血小板减少73.2%(30/41)、贫血58.5%(24/41)、手足综合征82.9%(34/41)、皮肤色素沉着56.1%(23/41)、疲劳或乏力48.8%(20/41)。上述各种毒副反应出现的时间不同、特点不一,95%出现在服药第1和第2周期。8例患者因3级毒副反应将索坦减量至12.5mg/日(主要为骨髓抑制、手足综合征、食欲减退和口腔溃疡),1例患者因4级血小板减少永久性停药。上述不良反应的处理措施包括降低药量、间断服用和其他合理的对症处理。结论索坦治疗甲磺酸伊马替尼治疗失败或不能耐受GIST患者的安全性良好,常见不良反应多为1/2级,而3/4级的发生率不到10%,因不良反应停药的比例仅为2.4%,通过降低剂量、暂停用药、积极预防及对症处理可以改善上述不良反应。

晚期或转移性胃肠道间质瘤治疗进展

胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是胃肠道最常见的间叶组织来源肿瘤,由于基因突变类型多样,GIST的临床病程特点和预后具有较大的异质性。虽然以伊马替尼为代表的一系列酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)给GIST患者带来了前所未有的生存获益,但多数患者仍会出现疾病进展或者转移的临床结局。对于晚期或转移性GIST,药物的选择以及手术在治疗中的适应证是近年来的研究热点。随着对GIST发病和耐药机制的研究深入,新型靶向药瑞派替尼、阿伐替尼以及作用于其他多通路靶点药物的出现使晚期/或转移性GIST的治疗模式更加精准化。本文就晚期或转移性GIST治疗现状及最新进展进行综述。

十二指肠间质瘤预后危险因素分析及不同手术治疗方式的远期预后比较

目的探讨影响十二指肠间质瘤(duodenal GIST)预后的相关因素及不同手术方式对其远期预后的影响。方法从SEER数据库中提取2000年-2019年诊断为duodenal GIST的患者资料,对其进行回顾性分析。采用多因素Cox比例风险模型,分析影响患者预后的危险因素,使用Kaplan-Meier法,分析内镜治疗组和外科手术组远期预后的差异。结果共纳入473例患者,中位年龄59岁,肿瘤中位直径50 mm。65.1%的患者初诊时为局限期,共390例(82.4%)患者接受手术治疗。其中,内镜治疗46例(11.8%),外科手术344例(88.2%)。多因素Cox分析结果显示,年龄>73岁、男性、肿瘤直径>67 mm和发生远处转移,是影响duodenal GIST患者肿瘤特异性生存期(CSS)的独立危险因素(P<0.05),接受内镜或外科手术治疗是CSS的独立保护因素(P<0.05)。内镜治疗和外科手术治疗duodenal GIST患者的长期生存率相似(5年CSS为84.8%和88.2%,10年CSS为80.1%和80.6%,15年CSS为71.2%和72.3%,P>0.05)。结论年龄>73岁、男性、肿瘤直径>67 mm和肿瘤出现远处转移,是影响duodenal GIST预后的独立危险因素,内镜治疗和外科手术治疗duodenal GIST的长期生存率无明显差异。

miR-17-5p在胃肠道间质瘤组织中的表达及其对GIST882细胞增殖与凋亡的影响

目的:探讨miR-17-5p在胃肠道间质瘤(gastrointestinal stromal tumor,GIST)组织中的表达及其对GIST882细胞增殖与凋亡的影响。方法:选取2019年5月至2020年5月广西医科大学第四附属医院胃肠外科手术切除的20例GIST患者的瘤组织及相应的瘤旁组织标本,以及GIST882细胞和人正常肠道上皮细胞HIEC为研究对象。荧光PCR-毛细管电泳测序法检测GIST标本中KIT基因突变情况。分别将miR-17-5p mimic和pc-KIT转染至GIST882细胞中。双荧光素酶报告基因实验验证miR-17-5p与KIT的靶向关系。qPCR和WB法检测GIST组织和细胞中miR-17-5p、KIT mRNA及蛋白的表达,CCK-8法、流式细胞术检测GIST882细胞的增殖、凋亡及细胞周期进程。结果:20例GIST组织中有15例患者发生KIT基因突变。与瘤旁组织比较,GIST组织中miR-17-5p表达水平显著降低、KIT mRNA表达水平显著升高(均P<0.01);与HIEC细胞比较,GIST882细胞中miR-17-5p表达显著降低、KIT m RNA和蛋白表达显著升高(均P<0.01)。过表达miR-17-5p可显著降低GIST882细胞的增殖能力(P<0.01)、提高细胞凋亡率(P<0.05)、sub-G1期和S期细胞比例显著增加(均P<0.05)、而G0/G1期的细胞比例显著减少(P<0.05),同时KIT蛋白表达水平明显降低(P<0.01)。双荧光素酶报告基因实验证实KIT是miR-17-5p的下游靶基因。同时过表达miR-17-5p和KIT对GIST882细胞的增殖、细胞周期进程和凋亡水平未产生明显影响。结论:过表达miR-17-5p可显著抑制GIST882细胞的增殖并诱导细胞凋亡,同时下调KIT蛋白的表达,miR-17-5p可能是治疗GIST的潜在靶标。

MMP-9表达与GIST生物学行为及血管生成拟态的关系探讨

目的:探讨基质金属蛋白酶-9(MMP-9)蛋白的表达与胃肠道间质瘤(GIST)危险度分级及血管生成拟态(VM)的关系。方法:采用免疫组化EnV ision二步显色法检测65例不同危险度分级(极低/低危,中危,高危/恶性)GIST中MMP-9蛋白的表达情况,并分析MMP-9蛋白表达与GIST危险度的关系以及GIST中MMP-9表达与VM存在的相关性。结果:随着GIST危险度的增加,MMP-9蛋白的阳性表达率、VM阳性率均逐渐升高,组间比较差异具有统计学意义(P<0.05)。GIST中VM的存在与MMP-9蛋白表达呈正相关关系(rS=0.312,P<0.05)。结论:MMP-9蛋白的表达和VM的存在可作为判断GIST危险度的参考指标。