肿瘤耐药相关蛋白及β-catenin在食管鳞状细胞癌中的表达及意义  被引量:10

Expression and significance of tumor drug resistance related proteins and β-catenin in esophageal squamous cell carcinoma

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作  者:甘思远[1] 钟雪云[1] 谢思明[1] 李素梅[2] 彭辉[3] 罗枫[1] 

机构地区:[1]暨南大学医学院病理学教研室,广东广州510632 [2]暨南大学医学院人体解剖学系,广东广州510632 [3]广东省中医院病理科,广东州510375

出  处:《癌症》2010年第3期323-329,共7页Chinese Journal of Cancer

基  金:国家"863"重大项目(No.2006AA02A403)~~

摘  要:背景与目的:随着化疗药物在肿瘤临床治疗中的广泛应用,肿瘤对化疗药物产生多药耐药性的问题越来越突出,已成为肿瘤联合化疗失败的主要原因之一。本研究检测β-catenin以及肿瘤耐药相关蛋白MRP2、P-gp、Bcl-2在食管鳞状细胞癌(esophageal squamous cellcar cinoma,ESCC)中的表达,探讨它们在ESCC的多药耐药发生发展中的作用和相互关系。方法:运用组织芯片技术、免疫组织化学方法以及图像分析技术检测582例ESCC及其癌旁294例正常黏膜、92例单纯细胞增生和87例不典型增生上皮组成的组织芯片中MRP2、P-gp、β-catenin及Bcl-2的表达情况,并分析其与各临床病理参数之间的关系。结果:MRP2、Bcl-2在ESCC中的累积光密度(integral optical density,IOD)值[分别为(195.7±175.9)×103和(90.5±112.5)×103]显著高于其在癌旁正常组织中的IOD值[分别为(104.8±86.1)×103和(25.2±46.6)×103],差异有统计学意义(P<0.01);P-gp、β-catenin在ESCC中的IOD值[分别为(57.7±75.5)×103和(32.0±47.0)×103]显著低于其在癌旁正常组织中的IOD值[分别为(114.8±106.6)×103和(46.1±35.7)×103],差异有统计学意义(P<0.01);随着ESCC的分化程度按高分化-中分化-低分化顺序依次改变,MRP2的IOD值依次递增,β-catenin在低分化ESCC中的IOD值大于其在中、高分化ESCC中的IOD值,Bcl-2在高分化ESCC中的IOD值低于其在中、低分化ESCC中的IOD值,差异有统计学意义(P<0.01);β-catenin、Bcl-2在ESCC浸润至黏膜层的病例的癌组织标本中的IOD值大于其在ESCC浸润至肌层或浆膜层的病例的癌组织标本中的IOD值,差异有统计学意义(P<0.01);有淋巴结转移的Bcl-2的IOD值显著高于无淋巴结转移(P<0.01);ESCC中P-gp的表达分别与MRP2、Bcl-2的表达呈明显正相关(r=0.288和r=0.253,P<0.01)。结论:P-gp与MRP2及Bcl-2可作为ESCC多药耐药的预测因子。β-catenin可能在ESCC的发生发展中起着重要作用。Background and Objective: As chemotherapy is generally used in the clinical treatment of cancer,the problem of multidrug resistance (MDR) of tumors against the chemotherapeutic agents becomes more and more serious. It has been the major cause for the failure of the chemotherapy. We detected the expressions of β-catenin and tumor drug resistance related proteins,MRP2,P-gp,and Bcl-2,in esophageal squamous cell carcinoma (ESCC) to explore their function and correlation in the occurrence and development of MDR in ESCC. Methods: We used the tissue microarray technique,immunohistochemistry,and image analysis methods to detect the expressions of MRP2,P-gp,β-catenin,and Bcl-2 proteins and analyze their relationships with clinical data in a ESCC tissue microarray consisting of 582 specimens of ESCC,294 specimens of normal mucosa,92 specimens of basal cell hyperplasia,and 87 specimens of dysplasia adjacent to cancer tissue. Results: The integral optical density (IOD) of MRP2 and Bcl-2,which was 195.7±175.9 (×10^3) and 90.5±112.5 (×10^3),respectively,was significantly higher in ESCC than in normal mucosa,which was 104.8±86.1 (×10^3) and 25.2±46.6 (×10^3),respectively ( P〈0.01). The IOD of P-gp and β-catenin,which was 57.7±75.5 (×10^3) and 32.0±47.0 (×10^3) respectively,was significantly lower in ESCC than in normal mucosa,which was 114.8±106.6 (×10^3) and 46.1±35.7 (×10^3),respectively ( P〈0.01). According to the following order,well differentiated—moderately differentiated—poorly differentiated,the IOD of MRP2 increased in ESCC ( P〈0.01). The IOD of β-catenin was higher in poorly differentiated ESCC than in well or moderately differentiated ESCC ( P〈0.01). The IOD of Bcl-2 was lower in well differentiated ESCC than in poorly and moderately differentiated ESCC ( P〈0.01). The IOD of β-catenin and Bcl-2 was higher in the ESCC of specimens with infiltration depths that were in membrane mucosa than those in the muscular laye

关 键 词:食管肿瘤 鳞状细胞癌 MRP2 P-GP Β-CATENIN Bcl-2 组织芯片 免疫组织化学 图像分析技术 

分 类 号:R735.1[医药卫生—肿瘤]

 

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