P16、CyclinD_1在胆管癌中的表达及意义

The Expressions and Significance of P16. Cyclin D_1 Proteins in Cholangiocarcinoma

[目的]通过对P16、CyclinD1蛋白在胆管癌中表达的检测,探讨其与胆管癌临床病理特征、淋巴结转移的关系。[方法]采用SP免疫组化方法检测45例胆管癌及10例正常胆管石蜡标本中P16、CyclinD1蛋白的表达,分析其表达与临床病理的关系。[结果]正常胆管中CyclinD1蛋白无阳性表达CyclinD1在胆管癌中阳性表达为66.67%,两者比较有显著差异（P〈0.01）.P16在正常胆管中均有表达（100%）,胆管癌中表达率37.78%,下调明显（P〈0.05）;P16与胆管癌临床分期相关（Ⅱ-Ⅲ与Ⅳ期比较P=0.015）;CyclinD1与胆管癌临床病理分期相关（Ⅱ-Ⅲ与Ⅳ期比较P=0.002）;P16与CyclinD1蛋白表达呈负相关（r=-0.374,P〈0.05）。[结论]P16基因的失活及其表达缺失和CyclinD1基因的激活及其过表达参与调节胆管癌的发生发展,且CyclinD1可以作为胆管癌组织分化的潜在生化标记,P16与CyclinD1存在互相抑制倾向,抑癌基因P16与癌基因CyclinD1可能协调参与调节胆管癌的发生发展。

[Objective]To investigate the relationship between the expression of P16 and Cyclin D1 proteins,and define the association of these proteins with clinicopathological characteristics,lymphatic metastasis of cholangiocarcinoma.[Methods]The expressions of P16 and Cyclin D1 protein were studied by streptoavidin-biotin complex.Paraffin sections from 45 cholangiocarcinomas and 10 normal（extrahepatic）bile duct specimens were examined.[Results]P16 expressed faintly in 100% of normal bile duct specimens,and no Cyclin D1 protein was detected in normal bile duct.The positive rates of P16 and Cyclin D1 in cholangiocarcinoma were 37.78%、66.67%respectively.The expression of P16 protein was significantly lower in cholangiocarcinoma than in normal bile ducts（P〈0.05）.The expression of Cyclin D1 protein was significantly higher in cholangiocarcinoma than in normal bile duct.P16 expression was associated with clinical stage significantly（P=0.015）,the positive rate of Cyclin D1 protein was associated with clinicopathological stage significantly（P=0.002）,Between two proteins studied,expression of P16 and Cyclin D1 was inversely correlated（r=-0.374,P〈0.05）.[Conclusion]Loss of P16 protein expression is a common event in the molecular oncogenesis and progression of extrahepatic bile duct carcinoma（EBDC）（P〈0.05）.Cyclin D1 over expression is a common event in the molecular oncogenesis and progression of EBDC（P〈0.01）.P16 protein expression is inversely correlated with Cyclin D1 expression.Loss of P16 protein expression and Cyclin D1 protein over expression act in cooperative ways to promote the molecular oncogenesis and progression of EBDC.