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.
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