Yu Guan-Zhen, Zhu Ming-Hua, Chen Ying, Ni Can-Rong, Li Fang-Mei
Department of Pathology, Changhai Hospital, Shanghai, 200433, PR China.
Ai Zheng. 2005 Nov;24(11):1398-403.
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.
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.
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).
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.
p53通路在胰腺癌的发生发展中起关键作用。然而,其触发因素及作用机制鲜有报道。本研究旨在探讨p53通路相关蛋白ATM、P53、Mdm2和P21(WAF/CIP1)在胰腺癌中的表达及临床意义。
采用组织芯片和免疫组化法检测167例胰腺癌标本及112例癌旁胰腺组织中ATM、P53、Mdm2和P21(WAF/CIP1)蛋白的表达。
胰腺癌组织中P53和Mdm2的阳性率高于癌旁胰腺组织(57.5%对6.3%,64.1%对5.4%,P<0.01),而ATM和P21(WAF/CIP1)的阳性率低于癌旁胰腺组织(67.7%对82.1%,39.5%对71.4%,P<0.05)。胰腺癌中ATM的表达与患者年龄有关(P<0.05)。P53的表达与肿瘤分化、淋巴结转移及神经侵犯有关(P<0.