AnxA1在食管鳞状细胞癌组织中的表达及意义

目的研究膜联蛋白A1(AnxA1)在食管鳞癌组织中的表达及其在食管鳞癌发生发展中的作用。方法应用免疫组化SABC法检测48例食管鳞癌、35例癌前病变(21例低级别上皮内瘤变、14例高级别上皮内瘤变)和18例正常对照组织中AnxA1的表达,并结合其临床病理资料进行分析。结果 AnxA1的阳性表达率在正常食管鳞状上皮组织、低级别上皮内瘤变组织、高级别上皮内瘤变组织及食管鳞状细胞癌组织中的表达分别为100%(18/18)、57.1%(12/21)、7.1%(1/14)和6.3%(3/48)。正常食管鳞状上皮组织AnxA1阳性表达率与其他三组AnxA1阳性表达率的差异有统计学意义(P0.05)。结论从食管正常组织到癌前病变组织以至鳞状细胞癌组织中,AnxA1的表达逐渐降低,提示其与食管鳞癌的早期癌变相关。     

Ki-67在Barrett食管中的表达及意义

目的 探讨Barrett食管患者食管黏膜组织中Ki-67的表达及意义.方法 应用免疫组化SP法测定45例经胃镜及活检确诊的Barrett食管(试验组)及30例正常食管黏膜组织(对照组)中Ki-67的表达.结果 Ki-67在Barrett食管中表达的阳性率为88.9％,在正常食管黏膜组织中表达阳性率为33.5％,两者比较差异有统计学意义(P＜0.05).结论 Barrett食管黏膜组织中Ki-67表达增强反映上皮细胞增殖活性异常增高,提示其在Barrett食管的肿瘤进程中起重要作用.     

硒结合蛋白1在食管鳞状细胞癌中的表达及意义

目的 探讨硒结合蛋白1(selenium binding protein 1, SBP1)在食管鳞状细胞癌(esophageal squamous cell carcinoma, ESCC) 和癌旁组织中的表达水平及其与ESCC临床病理特征的关系,初步评价SBP1在ESCC发生、发展中的作用及其意义. 方法收集17例ESCC患者的癌组织和癌旁组织,采用Western印迹法和RT-PCR检测SBP1的表达. 结果Western印迹和RT-PCR结果均显示,ESCC组织中SBP1表达水平明显低于癌旁组织 (P=0.000).SBP1的表达与ESCC患者的年龄、性别、分化程度、临床分期、淋巴结转移和浸润深度均无关(P＞0.05).结论 SBP1在ESCC组织中表达减少,它可作为正常食管鳞状上皮转变为癌组织的重要标志.     

食管鳞状细胞癌VEGF的表达及意义

肿瘤内新生血管可提供肿瘤生长必需的养料和转运其代谢产物,同时为肿瘤发生血性转移提供通道.新近研究表明,肿瘤血管形成是由多种生物活性因子调节控制的,其中血管内皮细胞生长因子(VEGF)在肿瘤新生血管形成中的作用尤为重要.     

Bmi-1和S100A4蛋白在食管鳞状细胞癌中的表达及其临床病理意义

目的:探讨Bmi-1和S100A4蛋白在食管鳞状细胞癌(ESCC)组织中的表达及其临床病理意义.方法:采用免疫组织化学法分别检测68例食管鳞状细胞癌、45例癌旁异型增生及36例正常食管黏膜组织中Bmi-1及S100A4蛋白的表达,并分析两者的表达水平与临床病理因素的关系.采用X2检验进行统计学分析.结果:Bmi-1蛋白在食管鳞状细胞癌、癌旁异型增生及正常黏膜组织中的阳性表达率分别为57.4%、48.9%、25.0%;S100A4蛋白的阳性表达率分别为48.6%、26.7%、13.9%,两者在组间的表达差异有统计学意义(P<0.01).食管鳞癌组织中Bmi-1和S100A4的蛋白表达与淋巴结转移及TNM分期均密切有关(P<0.05),而S100A4的蛋白表达还与肿瘤浸润深度有关(P<0.05).两者在食管鳞状细胞癌组织中的表达呈正相关(r=0.302,P<0.05).结论:Bmi-1及S100A4的蛋白表达与食管鳞状细胞癌发生发展密切相关,联合检测Bmi-1及S100A4两蛋白指标对食管鳞癌的预后判断具有重要的意义.     

食管鳞状细胞癌组织中β-catenin、LEF1的表达变化及其意义

目的 观察食管鳞状细胞癌(ESCC)组织β-连环蛋白(β-catenin)、淋巴细胞结合增强因子1(LEF1)的表达变化,并探讨其意义.方法 选取ESCC组织97例份、低级别上皮内瘤变组织19例份、高级别上皮内瘤变组织21例份、食管癌旁正常黏膜组织20例份,采用免疫组化SP法检测上述组织β-catenin、LEF1阳性...     

PUMA、Bcl-2在喉鳞状细胞癌组织中的表达及临床意义

目的观察喉鳞状细胞癌组织中PUMA、Bcl-2的表达,探讨其与喉癌发生发展及预后的关系。方法运用免疫组化sP法检测48例喉鳞癌组织及30例癌旁组织中PUMA、Bcl-2蛋白的表达,并分析二者的表达与临床病理参数的关系。结果PUMA和Bcl-2在喉癌组织中的表达阳性率分别为62．5％、43．8％,在喉鳞癌组织中的表达较喉癌旁组织低（P〈0．05）;PUMA的表达与肿瘤的组织学分化程度、有无颈淋巴结转移及术后生存期显著相关（P均〈0．05）,Bcl-2的表达与肿瘤的组织学分化程度、TNM分期及术后生存期显著相关（P〈0．05）;PUMA蛋白阳性组与PUMA蛋白阴性组的Bcl-2蛋白阳性率有统计学差异（P〈0．05）。结论PUMA、Bcl-2在细胞凋亡及肿瘤发生中起重要作用,对喉鳞癌的早期诊断和预后判断有重要意义。     

食管鳞癌组织中Survivin、Bcl-2蛋白的表达及意义

目的 探讨食管鳞癌中Survivin、Bcl-2蛋白的表达及其临床意义.方法 应用免疫组织化学SP法检测39例食管鳞癌组织、23例不典型增生组织及39例正常食管黏膜组织中Survivin、Bcl-2蛋白表达情况.结果 Survivin蛋白在癌组织中表达率为59.0%(23/39),Survivin蛋白的表达与肿瘤的临床分期、淋巴转移关系密切(P均＜0.05).Bcl-2蛋白在癌组织、癌旁不典型增生组织中的表达率为69.2%(27/39)、21.7%(5/23),Bel-2蛋白的表达与肿瘤组织的分化程度、临床分期、淋巴结转移有关(P均＜0.05);Survivin蛋白与Bcl-2蛋白表达呈正相关(r=0.46,P＜0.01).结论 Survivin蛋白和Bel-2蛋白的表达在食管癌的发生、发展中起重要作用.     

Survivin在肝细胞肝癌中的表达以及与Ki-67和bcl-2的关系

为研究Survivin在肝细胞癌(HCC)发病机制中所起的作用,用原位杂交和免疫组织化学的方法检测了HCC、肝硬化、正常肝组织Survivin mRNA表达及蛋白表达。同时,选择Ki-67和bcl-2,进行蛋白水平的检测,研究Survivin与两者的关系,从而在多基因变化与相互关系、增殖与凋亡的角度来探讨HCC的发生、发展机制。     

Ki-67和P21在肾上腺皮质癌中的表达及意义

目的　探讨肾上腺皮质癌 (ACC)中Ki 67和P2 1的表达及其意义。方法　采用免疫组化SP法和图像分析技术对 8例正常肾上腺组织、2 0例肾上腺腺瘤 (ACA)、19例肾上腺皮质癌中Ki 67、P2 1进行检测。结果　Ki 67和P2 1的表达在肾上腺腺瘤与肾上腺皮质癌间差异均有统计学意义 (P <0 .0 1,P <0 .0 5 )。Ki 67的表达与肾上腺皮质癌分期、浸润或转移、2年生存情况相关(P <0 .0 1) ,与肿瘤大小无关 (P >0 .0 5 )。P2 1的表达与肾上腺皮质癌的大小、分期、浸润或转移、2年生存情况均无显著相关 (P >0 .0 5 )。结论　Ki 67和P2 1对肾上腺皮质良恶性肿瘤具有重要的鉴别诊断作用 ,Ki 67可作为判断肾上腺皮质癌预后不良的指标。     

Bcl—2基因蛋白在食管异型增生组织和鳞癌中的表达变化及其意义

目的：目前食管癌的主要诊断方法有赖于病理学，至今尚无特异性肿瘤标志物，为此对找辅助食管癌早期诊断的分子标志物进行研究。方法：采用单克隆抗体免疫组化LSAB方法检测了BCl－2基因在EM、EED和SCCE中表达变化及其意义。结果：EM组无异常表达；EED组阳性表达率为65．7％，与EM组相比差异有显著性（P＜0．05），在EED中BCl－2蛋白表达增加主要发生在2和3级EED中（P＜0．05）；在SCCE中阳性表达率为77．1％，与EED组相比差异无显著性（P＞0．05），Bcl－2蛋白过表达主要与高分化的SCCE有关（P＜0.05）。结论：食管癌早期发生阶段存在Bcl－2基因表达异常，早期检测Bcl－2基因表达变化可能有助于食管癌早期发生的评估；Bcl－2基因对食管癌的进展不起重要作用。     

Expression of Bmi-1 and PAI-1 in esophageal squamous cell carcinoma

AIM:To determine the correlation between invasiveness,migration and prognosis in esophageal squamous cell carcinoma(ESCC)and expression of the B-cellspecific Moloney leukemia virus insert site 1(Bmi-1)and plasminogen activator inhibitor-1(PAI-1).METHODS:Eighty previously untreated patients who underwent surgical excision of ESCC were included.The expression of Bmi-1 and PAI-1 was examined immunohistochemically in formalin-fixed paraffinembedded primary tissue specimens.The relationships between the expression of Bmi-1 and PAI-1,the clinicopathologic features of ESCC,and the survival rate of ESCC patients were also discussed.The correlation between Bmi-1 and PAI-1 protein expression in ESCC was analyzed.The relationship between Bmi-1 and PAI-1expression and ESCC prognosis was evaluated using a Cox regression model and Kaplan-Meier survival curve analysis.RESULTS:The rates of positive Bmi-1 and PAI-1 expression in ESCC were higher than those in normal esophageal tissue(P<0.05).The expression of Bmi-1and PAI-1 was correlated with depth of invasion and lymph node metastasis(P<0.05),but not with patient age,tumor size or nationality(P>0.05).The expression of Bmi-1 was positively correlated with that of PAI-1(P<0.05).The 10-year overall survival rate for all patients was 20%(16∕80).Univariate KaplanMeier survival analysis showed that patients with high expression of esophageal PAI-1 and Bmi-1 had lower survival,however,the difference was not statistically significant.Cox multivariate analysis showed that PAI-1and Bmi-1 were not independent factors for survival rate,while the depth of tumor invasion and metastasis were independent factors affecting patient survival.CONCLUSION:The expression of Bmi-1 and PAI-1plays a role in ESCC progression,and may be used as a prognostic marker in ESCC.     

Expression of midkine and its clinical significance in esophageal squamous cell carcinoma

AIM: TO investigate the expression of midkine in esophageal squamous cell carcinoma (ESCC) and analyze its relationship with clinicopathological features. METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of midkine mRNA and protein in EC109 cells, respectively. Then the expression of midkine in 66 cases of ESCC samples were detected by immunohistochemistry using monoclonal antibodies against human midkine. RESULTS: Midkine was expressed in EC109 cell by RT-PCR and immunocytochemistry. The immunoreactivity was detected in 56.1% (37/66) of the ESCC samples. The expression of midkine was found in cytoplasm of tumor cells. Notably, the intensity of midkine was stronger at the area abundant in vessels and the invading border of the tumors. Midkine was more intensely expressed in well differentiated tumors (76.9%) than in moderately and poorly differentiated tumors (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant correlation between midkine expression and gender, age, clinical stage, lymph node metastasis or survival in ESCC. CONCLUSION: Midkine is overexpressed in ESCC. It may play a role in tumor angiogenesis and invasion. The expression of midkine is correlated with tumor cell differentiation in ESCC. The more poorly tumor cells differentiate, the weaker midkine expresses.     

口腔鳞癌组织中Cyclin D1、Ki-67基因的表达及意义

目的探讨口腔鳞癌组织中Cyclin D1、Ki-67基因蛋白表达与口腔鳞癌发生、发展的关系。方法取68份口腔鳞癌组织，用免疫组化法检测癌组织中Cyclin D1、Ki-67基因蛋白的表达，用积分PCR方法检测Cyclin D1的基因扩增。结果口腔鳞癌组织中Cyclin D1基因蛋白表达阳性36例(52．9％)，Ki-67基因蛋白表达阳性48例(70．5％)，Cyclin D1与Ki-67基因蛋白表达呈正相关(r=0．7861)，33份(48．5％)口腔鳞癌组织中Cyclin D1基因存在扩增，Cyclin D1基因扩增与Cyclin D1基因蛋白表达无相关性。Cyclin D1基因蛋白的表达与淋巴结转移有关，Ki-67基因蛋白的表达与肿瘤分化程度有关。结论Cyclin D1基因扩增及Ki-67基因蛋白表达水平可作为判断口腔鳞癌预后及其恶性程度的指标。     

c-IAP1在食管鳞癌中的表达及其对化疗敏感性的影响

目的:探讨食管鳞癌细胞凋亡抑制蛋白1(c-IAP1)表达与化疗敏感性的相关性.方法:食管鳞癌组织芯片免疫组织化学染色,分析食管鳞癌组织及其配对癌旁食管上皮中c-IAP1的表达和定位及其与肿瘤,临床分级的关系.免疫印迹分析食管癌细胞C-IAP1和Smac表达,用RNA干扰技术敲降Smac表达,MTT法检测细胞对化疗药物敏...     

Prognostic implications of FGFR1 and MYC status in esophageal squamous cell carcinoma

AIM To investigate the clinicopathological features and prognostic implications of combined MYC and fibroblast growth factor receptor 1(FGFR1) status in esophageal squamous cell carcinomas(ESCCs). METHODS All patients with ESCC(n = 180) underwent surgical resection at Seoul National University Hospital sometime between 2000 and 2013. A tissue microarray was constructed using cores obtained from representative tumor areas of formalin-fixed, paraffin-embedded tissue blocks. FGFR1 and MYC copy numbers were quantified using fluorescence in situ hybridization. The level of MYC expression was determined using immunohistochemistry. FGFR1 and MYC amplification status was compared between primary and metastatic lymph nodes. Univariate and multivariate survival analyses were performed according to adjuvant therapy status.RESULTS FGFR1 and MYC amplifications were observed in 21.4%(37/173) and 54.2%(91/168) of patients, respectively, while MYC expression was observed in 58.9%(106/180) of patients. There was a positive correlation between MYC amplification and overexpression(P = 0.002). Although FGFR1 amplification was not associated with MYC amplification or expression, 12.3%(20/163) of patients exhibited both FGFR1 amplification and MYC expression. There was also a correlation in FGFR1 amplification status between matched primary tumors and metastatic lymph nodes(P 0.001). MYC expression was higher in ESCCs with p T1(P 0.001) and in those with no lymph node metastasis(P = 0.023). MYC expression was associated with prolonged diseasefree survival(P = 0.036) and overall survival(OS)(P = 0.017) but was not an independent prognostic factor. FGFR1 amplification was an independent predictor for prolonged OS in all patients(P = 0.029) and in those who did not receive adjuvant therapy(P = 0.013). Combined FGFR1 amplification and MYC expression predicted better OS in patients who did not receive adjuvant therapy(P = 0.034) but not in those who did receive adjuvant therapy.CONCLUSION FGFR1 amplification and MYC expression have prognostic implications in resected ESCCs with respect to adjuvant therapy. The role of FGFR1-targeted therapy in ESCC remains to be explored.     

JAM3基因甲基化是食管鳞状细胞癌潜在的分子标志物

目的研究JAM3基因启动子区在食管癌中的甲基化情况及其表达调控机制,探讨JAM3基因启动子区异常甲基化作为食管鳞状细胞癌的潜在诊断标志物和治疗靶标。方法应用半定量RT-PCR、甲基化特异性PCR等技术对7个食管癌细胞系(KYSE140、KYSE150、KYSE410、KYSE450、COLO680N、KYSE520和TE13)、5例正常食管黏膜组织和83例原发性食管鳞状细胞癌组织进行分析。结果JAM3 mRNA在KYSE520、KYSE140、KYSE450细胞中高表达,这些细胞的JAM3基因启动子区呈非甲基化状态。JAM3 mRNA在KYSE410、COLO680N、TE13、KYSE150细胞中表达缺失,且其基因启动子区在这些细胞中呈完全甲基化。经过5-Aza-dc处理后,JAM3基因在KYSE410、COLO680N、TE13、KYSE150细胞中恢复表达。这些结果表明,JAM3在食管癌细胞中的表达受启动子区甲基化的调控。JAM3基因启动子区在5例正常食管黏膜组织中呈非甲基化状态(0/5),而在原发性食管鳞状细胞癌中其甲基化率为50.6%(42/83),且JAM3甲基化与肿瘤的位置相关(P<0.05)。结论JAM3在食管鳞状细胞癌中频繁发生甲基化,JAM3基因的表达受启动子区甲基化的调控,JAM3基因是潜在的食管癌诊断标志物和治疗靶标。     

趋化因子受体4在Barrett食管、食管腺癌和食管鳞状细胞癌中的表达及其意义

目的 了解趋化因子受体（CXCR4）在Barrett食管（BE）、食管腺癌和食管鳞状细胞癌中的表达,及其与病理分化程度、临床分期及淋巴结转移之间的关系.方法 应用免疫组织化学SP法对正常食管黏膜56例、BE 80例（其中伴多灶性异型增生22例）、食管腺癌25例和食管鳞状细胞癌组织48例标本中CXCR4的表达进行检测,并用仪器对表达结果进行图像分析,然后进行统计学分析.结果 （1）CXCR4在大部分BE、食管腺癌和食管鳞状细胞癌中呈阳性表达（其阳性率分别为78.8%、68.0%、83.3%）,3组间差异无统计学意义（P＞0.05）,而在正常食管黏膜组中呈阴性或弱阳性表达（阳性率为39.3%）,差异有统计学意义（P＜0.01）;（2）CXCR4在BE、食管腺癌和食管鳞状细胞癌的表达与性别、年龄、病变发生位置均无关（P＞0.05）;（3）CXCR4在BE无异型增生和BE伴多灶性异型增生组织标本中的表达差异无统计学意义（P＞0.05）;（4）CXCR4在食管腺癌高分化较中-低分化者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）;（5）CXCR4在食管鳞状细胞癌表达水平在肿瘤TNM分期的Ⅲ-Ⅳ级较Ⅰ-Ⅱ级者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）,高分化较中-低分化则明显更高（P＜0.01）.结论 CXCR4的表达上调可能是食管腺癌和鳞癌的一个普遍特征,与食管病理组织学类型无关,其表达在BE阶段就已上调,并与食管腺癌和鳞癌的分化程度,有无淋巴结转移和TNM分期有一定相关性.CXCR4的表达对BE、食管腺癌和鳞癌的诊断具有指导价值,有可能成为肿瘤治疗的一个新靶点.     

Alterations in cyclin D1 expression in esophageal squamous cell carcinoma in the Indian population

Purpose: The p16/cyclin D1/pRb pathway plays a critical role in tumourigenesis. We recently reported alterations in expression of tumour suppressor gene products, p16 and pRb in esophageal cancer. Knowledge of alterations in cyclin D1, a vital component of this pathway in esophageal carcinomas from the Indian subcontinent, where the etiology and pathogenesis may be confounded by various unique dietary and environmental factors, is presently scanty. In order to bridge the gap between the accentuating incidence of esophageal cancer and aberrations in the components of this vital pathway, we analysed cyclin D1 expression in esophageal squamous cell carcinoma in the Indian population. Method: Immunohistochemical analysis of cyclin D1 expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinomas (ESCC) (70 patients) and matched with histopathologically normal esophageal tissues from a distant site. The findings were correlated with clinicopathological parameters. Results: Overexpression of cyclin D1 was observed in the tumour nuclei in 41 out of 70 (59%) patients. We found concomitant alterations in 16 and cyclin D1 (p16⁻/CycD1⁺ phenotype) in 16 of the 70 patients (23%), while alterations of pRb and cyclin D1 (pRb⁻/CycD1⁺) were observed in 36 of the 70 (51%) patients of ESCCs. Cyclin D1 overexpression was significantly associated with the loss of p16 immunoreactivity (P=0.005). The pRb⁻ and p16⁻/pRb⁻/Cyc D⁺ phenotypes showed significant association with differentiation of the tumour (P=0.005, 0.05, respectively). Kaplan-Meier analysis for disease recurrence showed increased disease recurrence in cyclin D1 overexpressed patients. Median time to disease recurrence in the cyclin D1⁺ group was 15 months as against 18 months observed in the cyclin D1⁻ patients (P=0.067; log-rank test). Conclusion: Alterations in at least one of the components of the p16/cyclin D1/pRb pathway in majority of the 70 patients analysed herein, and concomitant alterations in all the three proteins in 19 patients (35%) underscore the critical role of this pathway in esophageal tumourigenesis. The results of the present study taken together with our previous findings on p16 and pRb alterations in ESCCs suggest that these alterations are not mutually exclusive and may cooperatively provide greater tumour growth advantage. The prognostic significance of alterations in the expression of these components cyclin D1, p16, and pRb remains to be established in a larger cohort. Received: 3 May 2000 / Accepted: 10 July 2000     

基质金属蛋白酶-9和组织金属蛋白酶抑制剂-1在食管鳞癌中的表达

目的探讨基质金属蛋白酶-9（MMP-9）和组织金属蛋白酶抑制剂-1（TIMP-1）在食管鳞癌中的表达及其临床意义。方法用免疫组化和Western blot法分别检测41例食管鳞癌患者的癌及相应正常组织中MMP-9和TIMP-1的表达变化。结果食管鳞癌组织中MMP-9阳性表达率与食管癌淋巴结及静脉转移有关；MMP-9的阳性表达率与表达量均显著高于TIMP-1；MMP-9和TIMP-1的表达呈负相关。结论MMP-9与食管鳞癌的侵袭转移有关，其机制可能与食管鳞癌组织中的MMP-9／TIMP-1平衡失调有关；MMP-9与TIMP-1联合检测有助于食管鳞癌生物学行为的判断。