食管鳞癌组织中cyclin D1和cyclin E的表达及意义

采用免疫组化法检测62例食管鳞癌组织中的细胞周期素（cyclin）D1、cyclin E,二者的阳性表达率分别为54.8%（34/62）、40.3%（25/62）,其表达与肿瘤长径、浸润深度、淋巴结转移、pTNM分期、肿瘤分化程度有关（P均〈0.05）;cyclin D1阳性表达组中cyclin E表达的阳性率高于cyclin D1阴性表达组（P〈0.05）;cyclin D1或cyclin E高表达的患者术后3 a生存率明显低于低表达者（P〈0.05）。认为cyclin D1和cyclin E是食管鳞癌预后不良的指标。     

食管鳞癌组织中hMLH1 mRNA的表达变化及意义

目的观察食管鳞癌组织中错配修复基因hMLH1 mRNA的表达变化,并探讨其临床意义。方法采用RT-PCR法检测60例食管鳞癌组织与癌旁组织中的hMLH1 mRNA。结果食管鳞癌组织中hMLH1 mRNA相对表达量（0.761 7±0.035 7）明显低于癌旁正常组织（1.025 2±0.047 4）,P〈0.05;hMLH1 mRNA的相对表达量与食管鳞癌分化程度、肿瘤浸润深度和淋巴结转移无关（P均〉0.05）,与病理分期有关（P〈0.05）。结论hMLH1 mR-NA表达缺失参与了食管鳞癌的发生或发展。     

BAG-1在食管鳞癌组织中的表达及意义

采用免疫组化S-P法检测92份食管鳞癌组织和20份正常食管黏膜中抗凋亡基因BAG-1的表达,并采用TNUEL法检测细胞凋亡指数。结果食管鳞癌组织BAG-1阳性表达率为70．6％（65／92）,明显高于正常食管黏膜组织15％（3／20）,差异有统计学意义BAG-1表达与癌组织分化程度、TNM分期、淋巴结转移密切相关;随BAG-1表达强度的增加,癌细胞凋亡指数逐渐降低。认为BAG-1能抑制癌细胞调亡,其表达与食管鳞癌的发生、发展密切相关,可作为食管鳞癌治疗的新靶点。     

食管鳞癌组织中Langerhans细胞水平及意义

采用免疫组化SP法检测39例正常食管上皮、23例不典型增生及39例食管鳞癌组织中S-100蛋白的表达,以观察其中Langerhans细胞（LC）的水平。结果正常食管上皮、癌旁不典型增生和鳞癌组织中LC阳性率分别为64.10%、30.43%、41.03%,P〈0.05。高、中、低分化鳞癌中LC阳性率分别为77.78%、45.45%、21.05%,P〈0.01;侵犯浅肌层、深肌层和纤维膜的鳞癌中LC阳性率分别为33.33%、40.00%、42.86%,P〈0.05;无和有淋巴转移的鳞癌中LC阳性率分别为53.85%、15.38%,P〈0.01。认为鳞癌中LC数量减少;LC数量减少程度与食管鳞癌的分化程度及是否发生淋巴转移有关,而与浸润深度无关。     

食管鳞癌和异型增生中TGFβ_1表达的意义

食管鳞癌和异型增生中ＴＧＦβ１表达的意义邓登豪１罗金燕２朱海杭１李登銮１王康敏２１扬州大学医学院附属苏北医院消化病研究室江苏省扬州市２２５００１２西安医科大学第二临床医学院ＳｕｂｊｅｃｔｈｅａｄｉｎｇｓＥｓｏｐｈａｇｅａｌｎｅｏｐｌａｓｍｓＣａｒ...     

食管鳞癌组织中胸苷磷酸化酶表达变化及意义

目的 观察食管鳞状细胞癌（ESCC）组织中胸苷磷酸化酶（TP）的表达变化,并探讨其与微血管密度（MVD）、细胞凋亡的关系.方法 采用免疫组化法检测155例ESCC患者肿瘤组织及癌旁组织中的TP、CD34以及ssDNA,CD34标记计数MVD,ssDNA阳性计算肿瘤细胞的凋亡指数（AI）.结果 155例ESCC患者中,肿瘤细胞TP表达阳性89例（57.4％）,基质细胞TP表达阳性104例（67.1％）；癌组织中平均MVD值为365条/mm2,其癌旁正常组织中平均MVD值为222条/mm,P＜0.01.155例中有154例（99.4％）检出凋亡阳性,AI均值为2.1％,二者无明显的相关性（P =0.074 7）.基质细胞TP阳性者MVD值明显高于TP阴性者（P＜0.01）,但肿瘤细胞TP是否阳性与MVD值无明显的关系；肿瘤细胞TP阳性者AI明显低于TP阴性者（P＜0.01）,基质细胞TP阳性者AI也低于TP阴性者,但差异并不显著.155例ESCC患者5年总生存率为32.5％.单因素分析显示,TNM分期越高、肿瘤细胞TP阳性、AI低是ESCC患者预后不佳的因素；多因素分析结果显示,TNM分期是ESCC独立预后评估因素.结论 TP可能通过增加微血管的生成及抑制肿瘤细胞凋亡等途径,在ESCC进展过程中起重要作用.     

食管鳞癌clusterin表达及其临床意义

目的:探讨食管鳞癌组织clusterin表达和单纯手术治疗前后外周血clusterin含量变化与食管鳞癌临床参数的相关性.方法:RT-PCR分析5对食管鳞癌及其远端切缘食管上皮中clusterin基mRNA表达水平;ELISA分析41例单纯手术治疗食管鳞癌患者治疗前后的血清clusterin蛋白表达水平及其与临床特征的相关性.结果:与正常食管上皮相比食管鳞癌组织中clusterin基因表达显著下降或缺失.食管鳞癌患者术前血清中clusterin含量明显低于术后血清含量(3.23 mg/Lvs 25.71 mg/L,P<0.0001).食管鳞癌患者术前血清clusterin含量与肿瘤大小相关(P<0.01),而与年龄、性别、分化程度、肿瘤分期、淋巴结转移.以及总蛋白、白蛋白、血糖、血脂和总胆红素浓度无关(r=-0.1334,-0.1602,0.2413,0.0389,-0.2882,均p>0.05).结论:clusterin基因在食管鳞癌组织中表达明显下调或缺失,血清clusterin含量明显降低,提示在食管鳞状细胞癌中clusterin基因可能具有潜在的抑癌基因作用,动态检测外周血clusterin含量有助于判断食管癌进展.     

食管鳞癌组织DNA和RNA含量测定及其临床意义

采用流式细胞仪对１４０例食管鳞癌患者的癌组织标本进行了ＤＮＡ和ＲＮＡ含量测定，并与１８例正常人的食管组织标本进行比较。结果显示，食管鳞癌组织ＤＮＡ异位体检出率（９０％）及ＲＮＡ含量均明显高于正常组织。病期晚、癌细胞分化差及有淋巴结转移者ＤＮＡ异倍体出现率高、ＲＮＡ含量增加，因此认为，ＤＮＡ和ＲＮＡ含量测定是一种判断食管鳞癌病期、恶性程度的客观指标，可为临床治疗提供依据，对完善肿瘤的组织学分级亦有重     

MTSS1及Gli1在食管鳞癌组织中表达及其相关性

目的 检测食管鳞癌组织中肿瘤转移抑制蛋白(MTSS)1及胶质瘤相关癌基因蛋白(Gli)1的表达水平,探讨MTSS1和Gli1的相关性。方法 应用免疫组织化学SP法和原位杂交方法检测136例食管鳞癌组织及其相应的96例癌旁不典型增生组织和136例正常食管黏膜组织中MTSS1、Gli1蛋白及mRNA的表达水平。结果 MTSS1蛋白和mRNA在食管鳞癌组织中的阳性表达率显著低于癌旁组织和正常食管黏膜组织,两两比较差异均有统计学意义(P<0.05)。Gli1蛋白和mRNA在食管癌组织中的阳性表达率显著高于癌旁不典型增生组织和正常食管黏膜组织,两两比较差异均有统计学意义(P<0.05)。有淋巴结转移组食管鳞癌组织中MTSS1蛋白及mRNA阳性表达率均显著低于无淋巴结转移组(P<0.05);有淋巴结转移组食管鳞癌组织中Gli1蛋白及mRNA阳性表达率均显著高于无淋巴结转移组(P<0.05);Gli1和MTSS1蛋白在食管鳞状上皮细胞癌组织中的表达呈负向相关(r=-0.422,P<0.05),Gli1和MTSS1 mRNA在食管鳞状上皮细胞癌组织中的表达亦呈负向相关(r...     

食管鳞癌患者血清中VEGF的表达变化及意义

目的观察食管鳞癌患者血清血管内皮生长因子（VEGF）的表达变化,并探讨其意义。方法采用ELISA法检测46例食管鳞癌患者和10名健康体检者外周静脉血血清中的VEGF。结果食管癌患者血清VEGF水平为（502.176±65.218）pg/ml,对照组为（311.648±40.984）pg/ml,两组相比,P〈0.01;根据肿瘤国际TNM分期标准：食管癌组Ⅰ期＋Ⅱ期者血清VEGF水平为（446.890±50.602）pg/ml,Ⅲ期者为（580.012±56.996）pg/ml,两组相比,P〈0.01;浸润深度T1＋T2者血清VEGF水平为（434.725±49.703）pg/ml,T3者为（503.504±68.500）pg/ml、T4者为（595.441±48.192）pg/ml,三者相比,P均〈0.01;有淋巴结转移者血清VEGF水平为（576.011±61.798）pg/ml,高于无淋巴结转移者的（464.340±68.639）pg/ml,P〈0.01。结论食管鳞癌患者血清VEGF表达升高,与肿瘤的发生、浸润深度、淋巴结转移情况及TNM分期相关。VEGF是食管鳞癌发生发展预后判断的一个有价值的依据。     

Definite intensity-modulated radiotherapy with concurrent chemotherapy more than 4 cycles improved survival for patients with locally-advanced or inoperable esophageal squamous cell carcinoma

We investigated which prognostic factor could improve survival for esophageal cancer patients who received definite concurrent chemoradiation (CCRT). Eighty patients with age ≥18, Karnofsky Performance Scale (KPS) ≥ 60, and clinical stage T1-4N0-3M0 esophageal squamous cell carcinoma were enrolled from July 2004 to December 2015. They underwent definite intensity-modulated radiotherapy (IMRT) with or without simultaneous integrated boost to the primary tumor, and reception of concurrent chemotherapy ≥ 1 cycle. The primary endpoints were overall survival (OS), locoregional progression-free survival (LRPFS) and distant metastasis-free survival (DMFS). The median follow-up duration for alive patients was 21.5 months. The rates of 2-, 3- and 5-year OS/LRPFS/DMFS were 23.8%/53.5%/49.3%, 19.1%/44.6%/49.3%, and 13.0%/44.6%/43.9%, respectively. Only the non-clinical complete response (non-cCR) after CCRT was an independent poor prognostic factor in OS (HR 3.101, 95% CI 1.535–6.265, p = 0.0016). Radiation dose >50.4 Gy and chemotherapy ≥4 cycles significantly predicted better LRPFS (p = 0.0361 and 0.0163, respectively). Poorly differentiated tumor and stage III disease have poor DMFS (p = 0.0336 and 0.0411, respectively), and chemotherapy ≥ 4 cycles was a better predictor (p = 0.0004). In subgroup analysis, patients who received radiation dose ≤50.4 Gy with concurrent chemotherapy ≥4 cycles had the best survival outcome with 1-, 2-, 3- and 5-year survival rates of 73.7%, 39.4%, 31.5% and 17.5%, respectively. In conclusion, definite radiotherapy with concurrent chemotherapy ≥4 cycles improved the survival for patients with inoperable or locally-advanced esophageal squamous cell carcinoma.     

Narrow-band imaging without magnification for detecting early esophageal squamous cell carcinoma

AIM:To compare narrow-band imaging(NBI)without image magnification,and chromoendoscopy with Lugol's solution for detecting high-grade dysplasia and intramu-cosal esophageal squamous cell carcinoma(SCC)in patients with head and neck cancer.METHODS:This was a prospective observational study of 129 patients with primary head and neck tumors consecutively referred to the Gastrointestinal Endoscopy Unit of Hospital das Clínicas,S?o Paulo University Medical School,Brazil,between August 2006 and Feb-ruary 2007.Con...     

Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region

AIM: To assess the prevalence of human papilloma virus (HPV) in esophageal squamous cell carcinoma (ESCC) in the south-eastern region of Poland.METHODS: The study population consisted of 56 ESCC patients and 35 controls. The controls were patients referred to our department due to other non-esophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology. In the ESCC patients, samples were taken from normal mucosa (56 mucosa samples) and from the tumor (56 tumor samples). Tissue samples from the controls were taken from normal mucosa of the middle esophagus (35 control samples). Quantitative determination of DNA was carried out using a spectrophotometric method. Genomic DNA was isolated using the QIAamp DNA Midi Kit. HPV infection was identified following PCR amplification of the HPV gene sequence, using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV. The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS: In tumor samples, HPV DNA was identified in 28 of 56 patients (50%). High risk HPV phenotypes (16 or/and 18) were found in 5 of 56 patients (8.9%), low risk in 19 of 56 patients (33.9%) and other types of HPV (37, 81, 97, CP6108) in 4 of 56 patients (7.1%). In mucosa samples, HPV DNA was isolated in 21 of 56 patients (37.5%). High risk HPV DNA was confirmed in 3 of 56 patients (5.3%), low risk HPV DNA in 12 of 56 patients (21.4%), and other types of HPV in 6 of 56 patients (10.7%). In control samples, HPV DNA was identified in 4 of 35 patients (11.4%) with no high risk HPV. The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56 (50%) vs 4 of 35 (11.4%), P < 0.001]. In esophageal cancer patients, both in tumor and mucosa samples, the predominant HPV phenotypes were low risk HPV, isolated 4 times more frequently than high risk phenotypes [19 of 56 (33.9%) vs 5 of 56 (8.9%), P < 0.001]. A higher prevalence of HPV was identified in female patients (71.4% vs 46.9%). Accordingly, the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7 (42.9%) vs 2 of 49 (4.1%), P < 0.05]. Of the pathological characteristics, only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27 (74.1%) vs 8 of 29 (27.6%) for ulcerative or protruding macroscopic type, P < 0.05]. The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation, phases in depth of tumor infiltration, grades of nodal involvement and stages of tumor progression.CONCLUSION: Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex, progressive, multifactorial and multistep esophageal carcinogenesis.     

Primary squamous cell carcinoma of the liver initially presenting with pseudoachalasia

Pseudoachalasia secondary to primary squamous cell carcinoma (SCC) of the liver is extremely rare and has not been reported until now. Here, we report a unique case of primary SCC of the liver initially presenting with progressive dysphagia along with short periods of significant weight loss. A 58-year-old man initially presented with progressive dysphagia along with significant weight loss over brief periods of time. The radiographic and manometric findings were consistent with achalasia. Subsequent esophagogastroduodenoscopy revealed a moderately dilated esophagus without evidence of neoplasm or organic obstruction. However, firm resistance was encountered while traversing the esophagogastric junction (EGJ), although no mucosal lesion was identified. Due to the clinical suspicion of the presence of a malignant tumor, endoscopic ultrasonography (EUS) and computed tomography scans of the chest and abdomen were obtained. A huge hepatic mass with irregular margins extending to the EGJ was found. EUS-guided fine-needle aspiration was performed, and the mass was diagnosed as a primary SCC of the liver by immunohistochemical staining.     

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。     

食管鳞癌组织诱导型一氧化氮合酶和增殖细胞核抗原的表达及意义

目的探讨食管鳞癌组织诱导型一氧化氮合酶（iNOS）和增殖细胞核抗原（PCNA）的表达与食管癌临床病理因素的关系。方法用免疫组化法检测2009年1至4月山东省泰安市中心医院52例食管鳞癌组织和20例癌旁正常组织iNOS与PCNA的表达,计数PCNA标记指数（PCNA LI）。食管鳞癌组织及癌旁正常组织iNOS蛋白阳性表达率、PCNA LI比较分别采用χ2检验、t检验;食管癌组织iNOS阳性表达者与iNOS阴性表达者PCNA LI比较采用t检验;不同临床病理因素食管鳞癌组织iNOS蛋白表达、PCNA LI比较分别采用χ^2检验、t检验、方差分析,进一步两两比较采用SNK-q检验;食管鳞癌组织iNOS蛋白与PCNA蛋白表达的关联性分析采用χ^2检验。结果食管鳞癌组织iNOS阳性表达率、PCNA LI均高于癌旁正常组织,且差异均有统计学意义[63.5%（33/52）与10.0%（2/20）比较,χ^2=14.455,P〈0.01;（53.29±14.55）与（2.65±1.82）比较,t=24.593,P〈0.05]。食管癌组织中,iNOS阳性表达者的PCNA LI高于iNOS阴性表达者,且差异有统计学意义[（60.89±9.98）与（40.08±11.53）比较,t=6.842,P=0.000]。不同临床分期、分化程度、有无淋巴结转移患者的食管鳞癌组织iNOS蛋白表达差异有统计学意义（χ^2=9.372,P=0.025;χ^2=12.784,P=0.002;χ2=6.361,P=0.012）。随着食管鳞癌组织癌细胞分化程度的降低PCNA LI升高,中分化和低分化的食管鳞癌组织PCNA LI明显高于高分化的食管鳞癌（q=6.000、7.378,P均〈0.05）。有淋巴结转移的食管鳞癌组织PCNA LI高于无淋巴结转移的食管鳞癌组织,且差异有统计学意义[（56.26±13.14）与（45.21±15.62）比较,t=2.556,P=0.014]。iNOS的表达与PCNA的表达有关联（χ^2=20.022,P=0.000）。结论 iNOS与PCNA蛋白在食管鳞癌组织中均有较高的阳性表达,且表达有关联。两者可能存在共同的激活机制,iNOS和PCNA蛋白表达与食管癌的恶性进程有关。     

pRB expression in esophageal mucosa of individuals at high risk for squamous cell carcinoma of the esophagus

AIM: To investigate the pRb expression in a large group of patients with history of chronic exposure to the main risk factors for development of squamous cell carcinoma of the esophagus. METHODS: One hundred and seventy asymptomatic individuals at high risk for esophageal squamous cell carcinoma (consumption of more than 80 g of ethanol and 10 cigarettes/d for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa. As a control group, specimens of esophageal mucosa obtained from 20 healthy subjects were also studied. Immunohistochemical assessment of the tissues was performed using a monoclonal antibody anti-pRB protein. RESULTS: Absence of the pRB staining, indicating loss of RB function, was observed in 33 (19.4%) of the individuals at risk for esophageal cancer, but in none of the healthy controls (P < 0.02). Loss of pRb expression increased in a stepwise fashion according to the severity of the histological findings (P < 0.005): normal mucosa (11/97 or 11.3%), chronic esophagitis (17/60 or 28.3%), low-grade dysplasia (3/10 or 30%), high-grade dysplasia 1/2 or 50%) and squamous cell carcinoma (1/1 or 100%). CONCLUSION: Our findings suggest that abnormal expression of the pRB protein may be implicated in the process of esophageal carcinogenesis. Additional studies are warranted to define the role of the pRBprotein as a biomarker for development of esophageal squamous cell carcinoma in individuals at high risk for this malignancy.     

Overexpression of Ets-like protein 1 in human esophageal squamous cell carcinoma

INTRODUCTION Esophageal cancer ranks among the 10 most frequent cancers in the world, with a predominant distribution in developing countries. It is one of the most common malignant tumors in China[1,2]. Our previous study showed that genetic susceptibili…     

食管鳞状细胞癌类器官的应用

类器官(organoid)作为一种新型的研究模型能够稳定保持肿瘤多细胞团的异质性特征,高度还原原位肿瘤组织的生理结构和功能。既能适用于高通量的临床药物筛选,提供个性化治疗的策略;又能构建病理模型,作为研究肿瘤发生、多个阶段发展和转移机制的有力工具。目前,食管、胃、肠、肝、胰、前列腺和乳腺等结构的类器官和相应的肿瘤类器官已有报道,开拓了体外培养的新平台。肿瘤类器官模型具有易操作、成本相对低廉且可以与其他先进技术相结合应用等明显优势,有望在相关领域广泛应用。本文对食管鳞状细胞癌类器官的培养技术及应用现状进行了总结。