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目的 分析结直肠癌组织中错配修复(MMR)蛋白MutL同系物1(MLH1)、MutS同系物2(MSH2)、MSH6和减数分裂后分离时增加2(PMS2)表达与临床病理特征的关联性,并进一步探讨MMR缺陷(dMMR)结直肠癌组织中4种MMR蛋白之间表达的相关性.方法 回顾性收集2018-03-27-2020-11-27皖南... 相似文献
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目的 探讨FHIT、MLH 1基因在结直肠癌组织中的表达及其意义。方法 采用免疫组化S P法检测 84例结直肠癌组织中FHIT、MLH 1基因表达。结果 FHIT、MLH 1基因在 84例结直肠癌中表达阳性率分别为 48.81%和 92 .86%。FHIT基因水平低或不表达与患者年龄、性别、肿瘤部位、组织学类型无关 (P >0 .0 5 ) ,而与肿瘤浸润深度、分化程度、Dukes分期和淋巴结转移有关 (P <0 .0 5 ) ;结直肠癌组织中FHIT基因表达与MLH 1基因表达无显著相关性 (P >0 .0 5 )。结论 FHIT基因参与了结直肠癌的演化和进展 ,是结直肠癌的 1个候选抑癌基因 ;结直肠癌组织中FHIT、MLH 1基因表达的关系还有待深入研究 相似文献
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[目的]评价错配修复基因hMLH1和hMSH2在结直肠癌中的表达及意义.[方法]经病理学确诊的结直肠癌手术切除标本85例,术前均未接受过放疗或化疗,免疫组化检测hMLH1和hMSH2蛋白表达情况.[结果]85例结直肠癌组中,hMSH2缺失率为69.4%(59/85),hMLH1蛋白缺失率为78.8%(67/85).hMSH2蛋白缺失率在T1、T2、T3和T4期结直肠肿瘤中的缺失率分别为50.0%、43.8%、71.1%和82.8%,随T分期增加而增加(x2=11.037,P=0.012).有淋巴结转移者的hMSH2蛋白缺失率达88.57% (31/35),而无淋巴结转移患者的hMSH2蛋白缺失率为56.0%(28/50) (x2=10.287,P=0.001).hMLH1蛋白缺失率与肿瘤分化程度和T分期相关,但与性别、年龄、肿瘤部位、N分期和M分期均无关.[结论]在结直肠癌组织中存在hMSH2和hMLH1蛋白缺失,且hMSH2和hMLH1蛋白缺失与肿瘤T分期和分化程度相关.检测hMLH1和hMSH2蛋白表达对预后判断有一定的参考价值. 相似文献
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Rb蛋白在结直肠癌中的表达及临床意义 总被引:1,自引:0,他引:1
目的 分析Rb蛋白表达与结直肠癌临床病理特征的关系。方法 应用免疫组化SABC法,检测44例结直肠癌癌中心、癌旁(距肿瘤边缘1cm)、切缘(距肿瘤边缘3cm以上)Rb蛋白表达情况,并分析Rb蛋白表达与结直肠癌临床病理特征的关系。结果 44例结直肠癌癌中心Rb蛋白表达为61.36%(27/44),癌旁粘膜为90.91%(40/44),切缘为97.73%(43/44);Rb蛋白表达与年龄、性别、肿瘤部位、大小及分化程度无显著相关,而与肿瘤临床分期及淋巴结转移显著相关。结论 Rb蛋白的表达与结直肠癌的部分临床病理特征密切相关,可能是判断结直肠癌预后的一项重要指标。 相似文献
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目的:对比观察胸腺瘤TdT在全自动免疫组织化学染色技术(automatic immunohistochemical staining techniques,AIST)和手工染色方法(manual staining method,MSM)中表达的差异性。方法:收集2015年-2016年大坪医院胸腺瘤手术标本21例,经石蜡包埋、切片、染色,显微镜下观察胸腺瘤TdT在AIST和MSM表达的差异。AIST采用Ventana公司生产的BenchMark XT,二抗检测系统分别采用UltraView Universal DAB Detection kit (简称UV)和Optiview DAB IHC Detection kit (简称OV)。结果:手工染色TdT阳性表达定位准确,染色强度强,背景清晰;AIST中采用UV二抗检测系统TdT染色虽然阳性定位准确,但TdT染色强度偏弱,背景不清晰,两者比较具有显著性差异(P<0.01)。优化染色方案后,改用OV二抗检测系统,TdT染色各项指标优于UV二抗检测系统,染色效果和手工相比,染色强度和阳性率一致。结论:任何抗体指标在行免疫组化前均需进行最适条件的摸索与优化,从而获得该抗体指标最佳的染色方案。 相似文献
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Allan JM Shorto J Adlard J Bury J Coggins R George R Katory M Quirke P Richman S Scott D Scott K Seymour M Travis LB Worrillow LJ Bishop DT Cox A;UK NCRI Colorectal Clinical Studies Group;Colorectal Cancer Study Group 《International journal of cancer. Journal international du cancer》2008,123(10):2456-2459
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Germline PMS2 mutation screened by mismatch repair protein immunohistochemistry of colorectal cancer in Japan 下载免费PDF全文
Kokichi Sugano Takeshi Nakajima Shigeki Sekine Hirokazu Taniguchi Shinya Saito Masahiro Takahashi Mineko Ushiama Hiromi Sakamoto Teruhiko Yoshida 《Cancer science》2016,107(11):1677-1686
Germline PMS2 gene mutations were detected by RT‐PCR/direct sequencing of total RNA extracted from puromycin‐treated peripheral blood lymphocytes (PBL) and multiplex ligation‐dependent probe amplification (MLPA) analyses of Japanese patients with colorectal cancer (CRC) fulfilling either the revised Bethesda Guidelines or being an age at disease onset of younger than 70 years, and screened by mismatch repair protein immunohistochemistry of formalin‐fixed paraffin embedded sections. Of the 501 subjects examined, 7 (1.40%) showed the downregulated expression of the PMS2 protein alone and were referred to the genetic counseling clinic. Germline PMS2 mutations were detected in 6 (85.7%), including 3 nonsense and 1 frameshift mutations by RT‐PCR/direct sequencing and 2 genomic deletions by MLPA. No mutations were identified in the other MMR genes (i.e. MSH2, MLH1 and MSH6). The prevalence of the downregulated expression of the PMS2 protein alone was 1.40% among the subjects examined and IHC results predicted the presence of PMS2 germline mutations. RT‐PCR from puromycin‐treated PBL and MLPA may be employed as the first screening step to detect PMS2 mutations without pseudogene interference, followed by the long‐range PCR/nested PCR validation using genomic DNA. 相似文献
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目的:通过对筛查结直肠癌DNA错配修复(mismatch repair,MMR)基因缺失两种最常用的检测方法的分析,寻找更为经济有效的检测策略。方法:分析新疆医科大学第一附属医院2018年9月至2019年9月收治并行手术的结直肠癌患者的肿瘤组织223例,采用免疫组织化学法检测平台检测MLH1、MSH2、PMS2、MSH6的表达缺失情况,PCR-毛细管电泳法检测肿瘤微卫星不稳定(microstatellites instability,MSI)状态。结果:在223例结直肠癌中,27例(12.1%)MMR蛋白表达缺失(MMR deficiency,dMMR),196例(87.9%)MMR蛋白表达完整(MMR proficient,pMMR)。MLH1、MSH2、MSH6和PMS2的缺失率分别为9.0%(20/223)、1.8%(4/223)、2.7%(6/223)和9.4%(21/223)。包含PMS2和MSH6的2种抗体试验筛查dMMR结直肠癌的灵敏度和特异度与4种抗体试验(MLH1、MSH2、PMS2、MSH6)的灵敏度和特异度均相同。微卫星高度不稳定(MSI-high,MSI-H)2... 相似文献
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M Koopman G A M Kortman L Mekenkamp M J L Ligtenberg N Hoogerbrugge N F Antonini C J A Punt J H J M van Krieken 《British journal of cancer》2009,100(2):266-273
A deficient mismatch repair system (dMMR) is present in 10–20% of patients with sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in early stage disease. Data on patients with advanced disease are scarce. Our aim was to investigate the incidence and outcome of sporadic dMMR in advanced CRC. Data were collected from a phase III study in 820 advanced CRC patients. Expression of mismatch repair proteins was examined by immunohistochemistry. In addition microsatellite instability analysis was performed and the methylation status of the MLH1 promoter was assessed. We then correlated MMR status to clinical outcome. Deficient mismatch repair was found in only 18 (3.5%) out of 515 evaluable patients, of which 13 were caused by hypermethylation of the MLH1 promoter. The median overall survival in proficient MMR (pMMR), dMMR caused by hypermethylation of the MLH1 promoter and total dMMR was 17.9 months (95% confidence interval 16.2–18.8), 7.4 months (95% CI 3.7–16.9) and 10.2 months (95% CI 5.9–19.8), respectively. The disease control rate in pMMR and dMMR patients was 83% (95% CI 79–86%) and 56% (30–80%), respectively. We conclude that dMMR is rare in patients with sporadic advanced CRC. This supports the hypothesis that dMMR tumours have a reduced metastatic potential, as is observed in dMMR patients with early stage disease. The low incidence of dMMR does not allow drawing meaningful conclusions about the outcome of treatment in these patients. 相似文献
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目的:探讨错配修复(mismatch repair,MMR)蛋白在左半结肠癌(left colon cancer,LCC)和右半结肠癌(right colon cancer,RCC)组织中的表达及其临床意义。方法:收集2014年01月至2017年12月间在我院接受手术治疗的368例结肠癌患者的临床病理资料,根据肿瘤原发部位分为LCC组与RCC组,分析MMR蛋白在LCC、RCC组织中的表达是否存在显著差异,同时探讨LCC、RCC的临床病理特征,并分析MMR蛋白对LCC、RCC预后的指导意义。结果:368例结肠癌组织中dMMR为25.8%。单因素分析结果显示,在不同肿瘤部位MMR蛋白的表达有显著性差异(P<0.05),RCC组中dMMR为17.4%,明显高于LCC组的8.4%;另外LCC、RCC在肿瘤直径、分化程度、组织学类型上存在统计学差异(均P<0.05)。进一步Logistic多因素分析发现:肿瘤直径≥5 cm(OR=1.762,95%CI:1.144~2.713,P=0.010)、dMMR(OR=2.672,95%CI:1.617~4.417,P=0.000)均为RCC的独立相关因素。Kaplan-Meier生存分析显示,dMMR组患者的OS显著高于pMMR组患者(P=0.035);经肿瘤部位分层分析发现,RCC组中dMMR患者的OS显著高于pMMR患者(P=0.004),但在LCC组中dMMR患者与pMMR患者的OS无显著性差异(P=0.951)。结论:RCC中dMMR发生率明显高于LCC,且仅在RCC中提示着较好的预后作用,而在LCC中无预后指示作用。 相似文献
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目的:探讨hMLH1和hMSH2基因在大肠腺瘤及其癌变中的作用,及其表达对细胞凋亡的影响。方法:采用免疫组织化学染色检测63例大肠腺瘤、20例腺瘤癌变和20例大肠癌组织hMLH1和hMSH2表达;同时采用TUNEL法检测其细胞凋亡指数(AI)。结果:大肠腺瘤、腺瘤癌变和大肠癌组织错配修复基因hMLH1、hMSH2的表达率逐渐降低,与正常大肠相比相差显著,随腺瘤不典型增生程度增加其阳性率逐渐降低;大肠腺瘤、腺瘤癌变和大肠癌中hMLH1表达缺失者细胞凋亡指数较显著高于其阳性者,且大肠腺瘤不典型增生Ⅰ、Ⅱ、Ⅲ级hMLH1-与hMLH1+组存在差异显著;而hMSH2-与hMSH2-间AI仅大肠腺瘤组有显著性差异,不典型增生Ⅰ、Ⅱ级组hMSH2-与hMSH2+间AI差异显著,而不典型增生Ⅲ级组hMSH2蛋白的表达阴性与阳性间AI无统计学差异。结论:DNA错配修复基因突变或功能缺失与大肠癌的发生有关,可能系大肠癌发生过程中的早期事件,且可能与大肠肿瘤细胞凋亡活性增加相关。 相似文献
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目的:探究错配修复基因MSH6对结直肠癌细胞的增殖、迁移和侵袭的影响及可能发生的机制。方法:根据美国国家生物信息技术中心(NCBI)中MSH6的基因序列构建靶向敲低MSH6的序列shMSH6-1、shMSH6-2和shMSH6-3,采用细胞转染技术敲低结直肠癌细胞中MSH6的表达,通过实时荧光定量 PCR 检测敲低效率并进行慢病毒包装,应用Western blot在细胞系中筛选MSH6高表达细胞系进行后续实验,应用CCK8检测细胞增殖能力,克隆形成实验检测细胞集落形成能力,伤口愈合和Transwell法检测细胞迁移和侵袭能力,通过Western blot方法检测上皮间充质相关蛋白的表达变化。结果:MSH6在结直肠癌细胞系中表达上调,其中RKO、SW620、LOVO细胞系上调明显,敲低MSH6明显限制了结直肠肿瘤细胞的增殖、迁移和侵袭,同时导致E-cadherin 蛋白水平增加,N-cadherin和Vimentin蛋白表达下降。结论:MSH6在结直肠癌中表达上调,敲低MSH6可抑制结直肠癌细胞的增殖、迁移和侵袭,诱导细胞发生凋亡并能够逆转EMT的发生。 相似文献
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Mutations of the 'minor' mismatch repair gene MSH6 in typical and atypical hereditary nonpolyposis colorectal cancer 总被引:1,自引:0,他引:1
Emanuela Lucci-Cordisco Valentina Rovella Stefania Carrara Antonio Percesepe Monica Pedroni Alfonso Bellacosa Oana Caluseriu Mara Forasarig Marcello Anti Giovanni Neri Maurizio Ponz de Leon Alessandra Viel Maurizio Genuardi 《Familial cancer》2001,1(2):95-101
Mutations of the mismatch repair (MMR) genes MLH1 and MSH2 are associated with hereditary nonpolyposis colorectal cancer (HNPCC), a highly penetrant autosomal dominant condition characterized by hypermutability of short tandemly repeated sequences in tumor DNA. Mutations of another MMR gene, MSH6, seem to be less common than MLH1 and MSH2 defects, and have been mostly observed in atypical HNPCC families, characterized by a weaker tumor family history, higher age at disease onset, and low degrees of microsatellite instability (MSI), predominantly involving mononucleotide runs. We have investigated the MSH6 gene sequence in the peripheral blood of 4 HNPCC and 20 atypical HNPCC probands. Two frameshift mutations within exon 4 were detected in 2 patients. One mutation was found in a proband from a typical HNPCC family, who had developed a colorectal cancer (CRC), a gastric cancer and a rectal adenoma. The CRC and the adenoma showed mild MSI limited to mononucleotide tracts, while the gastric carcinoma was microsatellite stable. The other mutation was detected in an atypical HNPCC proband, whose CRC showed widespread MSI involving both mono- and dinucleotide repeats. The phenotypic variability associated with MSH6 constitutional mutations represents a complicating factor for the optimization of strategies aimed at identifying candidates to MSH6 genetic testing. 相似文献
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Jose G. Monzon Carol Cremin Linlea Armstrong Jennifer Nuk Sean Young Doug E. Horsman Kristy Garbutt Chris D. Bajdik Sharlene Gill 《International journal of cancer. Journal international du cancer》2010,126(4):930-939
Lynch syndrome is defined by the presence of germline mutations in mismatch repair (MMR) genes. Several models have been recently devised that predict mutation carrier status (Myriad Genetics, Wijnen, Barnetson, PREMM and MMRpro models). Families at moderate‐high risk for harboring a Lynch‐associated mutation, referred to the BC Cancer Agency (BCCA) Hereditary Cancer Program (HCP), underwent mutation analysis, immunohistochemistry and/or microsatellite testing. Seventy‐two tested cases were included. Twenty‐five patients were mutation positive (34.7%) and 47 were mutation negative (65.3%). Nineteen of 43 patients who were both microsatellite stable and normal on immunohistochemistry for MLH1 and MSH2 were also genotyped for mutations in these genes; all 19 were negative for MMR gene mutations. Model‐derived probabilities of harboring a MMR gene mutation in the proband were calculated and compared to observed results. The area under the ROC curves were 0.75 (95%CI; 0.63–0.87), 0.86 (0.7–0.96), 0.89 (0.82–0.97), 0.89 (0.81–0.98) and 0.93 (0.86–0.99) for the Myriad, Barnetson, Wijnen, MMRpro and PREMM models, respectively. The Amsterdam II criteria had a sensitivity and specificity of 0.76 and 0.74, respectively, in this cohort. The PREMM model demonstrated the best performance for predicting carrier status based on the positive likelihood ratios at the >10%, >20% and >30% probability thresholds. In this referred cohort, the PREMM model had the most favorable concordance index and predictive performance for carrier status based on the positive LR. These prediction models (PREMM, MMRPro and Wijnen) may soon replace the Amsterdam II and revised Bethesda criteria as a prescreening tool for Lynch mutations. 相似文献