Lymph Node Metastasis in Early Signet Ring Cell Carcinoma:Endoscopic Mucosal Resection

Objective:To identify clinicopathological factors predictive of lymph node metastases(LNM)in early signet ring cell carcinoma(SRC),and further to expand the possibility of using endoscopic mucosal resection(EMR)for the treatment of early SRC.Methods:Data from 27 surgically treated patients with early SRC were collected,and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses.Results:In the ...     

E-Cadherin(CDH1)基因胚系突变与胃癌风险的研究

背景与目的： 检测E_Cadherin (CDH1) 基因在家族性胃癌中的突变情况以探讨CDH1基因胚系突变在家族性胃癌中的作用。 方法： 采用聚合酶链反应(Polymerase chain reaction, PCR)、变性高效液相色谱分析(Denaturing high_performance liquids chromatography, DHPLC)和直接测序法对CDH1基因进行全基因筛查,检查80名胃癌患者的CDH1基因突变情况,其中62例有家族史。同时检测80例正常人CDH1基因,进行分析比较。 结果： 2.5％(2/80)的胃癌患者检出CDH1基因错义突变Thr340Ala(杂合型),在80例正常人中未检出这一突变;第13外显子上游(内含子)第13位碱基检出多态位点IVS(13)_13T→C,这一多态性存在于12.5％(10/80)的胃癌患者和15.0％(12/80)的正常对照,两组差异无统计学意义;23.8％(19/80)的胃癌患者中检出同义突变Asn751Asn,相同的突变存在于8.8％(7/80)的正常对照。统计结果表明,胃癌患者中CDH1基因 Asn751Asn检出率高于正常人群(P<0.05),这种差异主要表现在高年龄组胃癌患者(P<0.01)。 结论： CDH1基因胚系突变在家族性胃癌中不是频发事件,但多态位点Asn751Asn的存在可使携带者胃癌发病风险增高,可能是部分癌高发家族癌症发生的原因之一。     

PTEN/MMAC1 Mutations in Hepatocellular Carcinomas: Somatic Inactivation of Both Alleles in Tumors

Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1-bp insertion at codon 83–84 in exon 4 and two 4-bp deletions, both at codon 318–319 in exon 8; two C-to-G transversion mutation, both at -9 bp from the initiation codon in the 5'non-coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors.     

Methylation of RASSF1A and CDH13 Genes in Individualized Chemotherapy for Patients with Non-small Cell Lung Cancer

Background: This study aimed to evaluate the methylation of RASSF1A and CDH13 gene promoter regions as a marker for monitoring chemotherapeutic efficacy with personalized medicine for patients with NSCLC, in the hope of providing a new direction for NSCLC individualized chemotherapy. Materials and Methods: 42NSCLC patients and 40 healthy controls were included. Patient blood samples were collected in the whole process of chemotherapy. Methylation of RASSF1A and CDH13 gene promoter regions was detected by the methylation specific polymerase chain reaction (MSP). Results: The rate of RASSF1A and CDH13 gene methylation in 42 cases of NSCLC patients was significantly higher than in 40 healthy controls (52.4% to 0.0%, 54.8% to 0.0%, p<0.05). After the chemotherapy, the hyper-methylation of RASSF1A and CDH13 genes in PR group and SD group decreased significantly (p<0.05), and was significantly different from that in PD group (p<0.05), but not as compared with healthy controls (P>0.05). With chemotherapy, RASSF1A and CDH13 promoter region methylation rate in 42 cases of patients showed a declining trend. Conclusions: The methylation level of RASSF1A and CDH13 gene promoter region can reflect drug sensitivity of tumors to individualized treatment.     

Bmi1、EZH2在食管鳞癌中的表达及其临床价值

目的 探讨Bmi1与EZH2共同高表达对食管鳞癌的影响.方法 回顾性分析82例食管鳞癌患者的临床资料,考察Bmi1与EZH2在食管鳞癌组织中的表达情况及其对食管鳞癌患者生存率的影响,并进一步分析Bmi1与EZH2的表达情况对食管鳞癌的影响是否存在关联性.结果 肿瘤组织Bmi1与EZH2的IS得分均明显高于癌旁组织(P<0.05);Bmi1高表达组患者2~5年及5年生存率较Bmi1低表达组低(P<0.05),EZH2高表达组患者各时间段生存率与低表达组比较差异无统计学意义(P>0.05);Bmi1与EZH2共同高表达组与其他组的食管鳞癌患者的P16表达情况差异无统计学意义(P>0.05).结论 Bmi1与EZH2与食管鳞癌的发生和发展有密切联系,且影响食管鳞癌患者的预后,Bmi1与EZH2共同高表达是食管鳞癌发生的独立危险因素.     

食管鳞癌中癌-睾丸抗原NY-ESO-1及MAGE-1的表达

目的研究NY-ESO-1及MAGE-1蛋白在食管鳞癌中的表达，分析其与肿瘤临床病理参数的关系，为食管癌的免疫治疗提供理论依据。方法构建组织芯片并结合免疫组化的方法，检测NY-ESO-1及MAGE-1蛋白在113例食管鳞癌及10例正常食管黏膜中的表达。结果10例正常食管黏膜均不表达NY-ESO-1及MAGE-1蛋白，而其在食管鳞癌组织芯片109例有效标本中的阳性率分别为29.4%和37.4%（32/109，41/109），阳性部位均位于细胞质。其中，59例至少表达1种CT抗原，占总数的54.1%（59/109），13例同时表达2种CT抗原，占11.9%（13/109）；NY-ESO-1及MAGE-1蛋白的表达主要集中在肿瘤细胞分化较好的I级和II级食管鳞癌，阳性率有显著性差异（P〈0.01），与肿瘤的大小，浸润深度及有无淋巴结转移无关（P〉0.05）。结论NY-ESO-1及MAGE-1可作为食管癌免疫治疗的靶标之一，含有CT抗原的疫苗可用于食管癌患者的免疫治疗。     

放射线诱导hEgr-1-CD对鼻咽癌CNE放射增敏作用的研究

目的 研究放射线诱导hEgr-1-CD自杀基因前药系统对鼻咽癌CNE细胞株放射增敏作用。方法 将pcDNA3.1（＋）Egr-1-CD利用脂质体转染的方法 转染入鼻咽癌细胞株,给予不同剂量的X线照射观察基因表达与放射的剂量效应关系,观察不同的放射线及不同剂量的前药对鼻咽癌细胞的杀伤效应。结果 电离辐射可诱导增强自杀基因阳性鼻咽癌CNE细胞株中CD基因的表达,电离辐射与前药5-Fc的联合应用大大增强了对自杀基因阳性细胞的杀伤作用,其杀伤作用大于单独自杀基因前药系统和单独照射。结论 hEgr-1-CD自杀基因前药系统对鼻咽癌CNE细胞株有放射增敏作用,其与放射联合应用对CNE细胞有明显的协同杀伤作用。     

TMS1/ASC基因CpG岛甲基化与膀胱移行细胞癌发生的关系

目的检测抑癌基因TMS1/ASC启动子区5′CpG岛甲基化状态及其在膀胱移行细胞癌（BTCC）中mRNA和蛋白表达水平。方法应用MSP技术检测膀胱移行细胞癌中TMS1/ASC基因启动子区甲基化状态,RT-PCR和Western blot法分别检测其mRNA和蛋白表达水平。结果TMS1/ASC基因在正常膀胱组织中未发生甲基化,而在癌组织中甲基化频率为46.9%（15/32）,并且随着肿瘤分级、分期的增加,其甲基化水平逐渐升高（χ^2=23.106,P〈0.05）。在15例启动子异常甲基化的BTCC标本中,14例同时伴有TMS1/ASC基因表达缺失或下调,两者存在明显的相关性（γ=0.5842,P〈0.05）。TMS1/ASC mRNA和蛋白表达在正常膀胱组织和BTCC组织中分别为81.3%（26/32）、18.8%（6/32）（P〈0.01）,不同病理分级、临床分期间差异有统计学意义（P〈0.05）。结论TMS1/ASC基因启动子区异常甲基化可能导致该基因转录表达失活,使其mRNA和蛋白表达减少,甚至缺失,这可能是膀胱癌发生、发展的原因之一。     

P33ING1、p53基因在膀胱移行细胞癌中的表达及其意义

目的探讨抑癌基因P33ING1在膀胱移行细胞癌中的表达及其与p53蛋白表达的相关性。方法采用免疫组化S-P法,检测83例膀胱移行细胞癌及11例正常膀胱黏膜组织中P33ING1、p53的表达。结果83例膀胱移行细胞癌组织中P33ING1蛋白阳性表达率为59．03％,而正常膀胱黏膜组织中P33ING1蛋白阳性表达率为90．90％。P33ING1蛋白表达与膀胱移行细胞癌的WHO肿瘤分级相关。根据Spearman相关分析表明P33INGI蛋白表达与p53蛋白表达呈正相关关系（P〈0．05）。结论P33ING1基因可能在膀胱移行细胞癌的发生、发展过程中起重要作用,P33ING1与p53基因具有协同作用,同时检测p53和P33ING1表达水平,对膀胱癌的诊断、治疗和预后判断可能具有积极意义。     

Somatic Mutations of the PTEN/MMAC1 Gene in Fifteen Japanese Endometrial Cancers: Evidence for Inactivation of Both Alleles

Loss of heterozygosity (LOH) of chromosome 10q is observed in approximately 40% of endometrial cancers. Mutations in PTEN/MMAC1 , a gene recently isolated from the 10q23 region, are responsible for two dominantly inherited neoplastic syndromes, Cowden disease and Bannayan-Zonana syndrome. Somatic mutations of this gene have also been detected in sporadic cancers of the brain, prostate and breast. To investigate the potential role of this putative tumor suppressor gene in endometrial carcinogenesis as well, we examined 46 primary endometrial cancers for LOH at the 10q23 region, and for mutations in the entire coding region and exon-intron boundaries of the PTEN/MMAC1 gene. LOH was identified in half of the 38 informative cases, and subtle somatic mutations were detected in 15 tumors (33%). Our results suggest that of the genes studied so far in endometrial carcinomas, PTEN/MMAC1 is the most commonly mutated one, and that inactivation of both copies by allelic loss and/or mutation, a pattern that defines genes as "tumor suppressors,'contributes to tumorigenesis in endometrial cancers.     

Characterization of PD-1 and PD-L1 Expression in Papillary Renal Cell Carcinoma: Results of a Large Multicenter Study

BackgroundProgrammed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce.Patients and MethodsPatients’ sample collection was a joint collaboration of the nationwide PANZAR consortium – a multicenter study. Medical history and tumor specimens were collected from 245 and 129 patients with pRCC types 1 and 2, respectively. Expression of PD-1 and PD-L1 was determined by immunohistochemistry in pRCC and tumor-infiltrating mononuclear cells.ResultsOf 374 pRCC specimens, 204 type 1 and 97 type 2 were evaluable for PD-1 and PD-L1 expression analysis. In total, PD-1 and PD-L1 expression were found in 8 (4.9%) of 162 and 12 (7.2%) of 166 evaluable pRCC type 1 specimens. Comparably, PD-1 and PD-L1 expression were found in 2 (2.4%) of 83 and 5 (6.2%) of 81 evaluable pRCC type 2 specimens. Hardly any clinically relevant associations between PD-1 and PD-L1 positivity and clinicopathologic or clinical courses were observed, neither in pRCC type 1 nor type 2.ConclusionThe analysis of a large pRCC cohort from a multicenter consortium revealed no impact of PD-1/PD-L1 expression on prognosis in patients with pRCC with predominantly limited disease status, neither for type 1 nor type 2. However, the impact of PD-1 and PD-L1 in more advanced pRCC disease needs further elucidation.     

人食管鳞癌EC9706细胞线粒体DNA中ND1基因突变的检测及意义

目的通过对人食管鳞癌EC9706细胞线粒体DNA（mtDNA）中ND1基因进行检测,分析其基因突变的意义。方法培养人食管鳞癌EC9706细胞,提取其mtDNA中的ND1基因,并测序。结果测序发现,人食管鳞癌EC9706细胞mtDNA中ND1基因的3971处出现点突变,由C突变为T。结论人食管鳞癌EC9706细胞中mtDNA的ND1基因的突变与食管癌发生、发展关系密切。     

结肠癌组织中ERCC1表达及其临床意义

目的探讨结肠癌组织中ERCC1表达及其临床意义。方法应用采用免疫组化（即用型二步法）检测其ERCC1表达水平,术后均以奥沙利铂为主的方案化疗,所有入组患者随访3年以上。结果结肠癌组织中ERCC1表达阳性率为51%。ERCC1表达与患者性别、年龄、病理类型无明显相关性;与肿瘤局部浸润有关,但与淋巴结转移及TNM分期无明显相关性;ERCC1阴性患者,术后经奥沙利铂为主的方案化疗后2、3、4和5年生存率均高于阳性患者,经Logrank检验,两者有显著性差异;Cox回归分析显示ERCC1表达为结肠癌患者独立预后因素。结论ERCC1蛋白表达阴性患者应用以奥沙利铂为主的方案化疗可能获得生存受益;ERCC1表达水平可作为结肠癌患者术后辅助化疗方案的选择及预后判断的指标之一。     

在非小细胞肺癌组织中DPC4和P21WAF1/CIP1蛋白的表达

目的 探讨DPC4、P21WAF1/CIP1在非小细胞肺癌组织中的表达及与肺癌生物学行为及预后的关系.方法 利用免疫组组织化学S-P法检测60例非小细胞肺癌组织及30例癌旁正常肺组织中DPC4及P21WAF1/CIP1蛋白的表达.结果 DPC4在肿瘤组织中阳性表达率为65%(39/60),与癌旁正常肺组织的阳性表达率90%(27/30)相比,DPC4阳性表达显著降低,差异有统计学意义(P＜0.05);DPC4与淋巴结转移、临床分期相关(P＜0.05),而与病理类型、组织学分级无关(P＞0.05).P21WAF1/CIP1在肿瘤组织中阳性表达率为68.3%(41/60),与癌旁正常肺组织的阳性表达率6.7%(2/30)相比,差异有统计学意义(P＜0.05);P21WAF1/CIP1与组织学分类、临床分期、是否有淋巴结转移等无关(P＞0.05).结论 DPC4、P21WAF1/CIP1异常表达可能参与了NSCLC的发生发展,联合检测二者有助于判断肺癌的恶性程度及预后.