摘要
背景与目的:P53通路在胰腺癌的发生发展中发挥重要作用,然而关于此通路是如何启动、如何作用的研究较少,故本研究探讨P53通路相关基因(ATM/P53/Mdm2/P21WAF/CIP1)蛋白在167例胰腺癌发生、发展中及与预后的关系。方法:应用组织芯片和免疫组化法研究ATM、P53、Mdm2和P21WAF/CIP1在167例胰腺外分泌恶性肿瘤和101例癌旁组织以及11例胰腺良性病变中的表达情况。结果:ATM、P53、Mdm2和P21WAF/CIP1在癌组织中的阳性率分别为67.7%、57.5%、64.1%和39.5%,在非癌组织中阳性率分别为82.1%、6.3%、5.4%和71.4%。与非癌组织相比,癌组织中P53和Mdm2表达明显升高(P<0.01),而ATM和P21WAF/CIP1的表达明显降低(P<0.05)。P21WAF/CIP1的阳性表达与发病年龄、神经受累显著相关(P<0.05);P53的阳性表达与肿瘤的分化、淋巴结转移和神经受累均显著相关(P<0.05);Mdm2的阳性表达与肿瘤的分化显著相关(P<0.05);ATM的阳性表达与年龄相关(P<0.05);四者阳性表达两两之间统计学上具有关联性(P<0.05)。44例获1年以上随访者中ATM+/Mdm2+/P53+P21WAF/CIP1+、ATM-/Mdm2-/P53-/P21WAF/CIP1-、ATM+Mdm2+/P53+分别为9、11、5例,平均生存期依次为9.3、26.1、20月。Kaplan-Meier分析显示全阳性组预后较全阴性组和P21阴性组预后差。结论:P53和Mdm2的过表达以及ATM和P21WAF/CIP1的缺失表达可能会导致胰腺癌的形成和进展;4种蛋白可能以ATM-P53-Mdm2-P21WAF/CIP1通路的方式作用于细胞的转化和肿瘤的形成;联合检测P53和Mdm2的表达可用于评定胰腺癌的恶性程度。
BACKGROUND ＆ OBJECTIVE： P53 pathway plays a critical role in carcinogenesis of pancreatic carcinoma. However, its trigger and function mechanisms have seldom been reported. This study was to investigate the expression and clinical significance of P53 pathway-related proteins ATM, P53, Mdm2, and P21^WAF/CIP1
in pancreatic carcinoma. METHODS.. The expression of ATM, P53, Mdm2, and P21^WAF/CIP1
proteins in 167 specimens of pancreatic carcinoma and 112 specimens of non-cancer pancreatic tissues was detected by tissue microarray and immunohistochemistry. RESULTS. The positive rates of P53 and Mdm2 were higher in pancreatic carcinoma than in non-tumor pancreatic tissues （57.5% vs. 6.3%, 64.1% vs. 5.4%, P〈0.01）, while the positive rates of ATM and P21^WAF/CIP1
were lower in pancreatic carcinoma than in non-tumor pancreatic tissues （67.7% vs. 82.1%, 39.5% vs. 71.4%, P〈0.05）. ATM expression in pancreatic carcinoma was related to patients＇ age （P〈0.05）. P53 expression was related to tumor differentiation, lymph node metastasis, and nerve involvement （P〈0.05）. Mdm2 expression was related to tumor differentiation （P〈0.05）. P21^WAF/CIP1
expression was related to patients＇ age and nerve involvement （P〈0.05）. There were statistical correlations between these 4 proteins （P〈0.05）. CONCLUSIONS. Overexpression of P53 and Mdm2 and loss of ATM and P21^WAF/CIP1
expression may contribute to the tumorigenesis and development of pancreatic carcinoma. The 4 proteins may affect cell transformation and tumorigenesis through ATM-Mdm2-P53-P21^WAF/CIP1
pathway. Co-detection of P53 and Mdm2 can be used to evaluate the differentiation of pancreatic carcinoma.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2005年第11期1398-1403,共6页
Chinese Journal of Cancer
