The Expression And Significance Of Transforming Growth Factor β₁, β Receptor Ⅱ And P27～(kipl) Protein In Cholangiocarcinoma

Objectives The aim of the study was to investigate the relationship among the expression of the TGF-3i> T3RII and p27kipl and to explore the possible mechanisms by which they effect carcinoma of bile duct.Methods Immunohistochemical S-P method was used to examine the expression of TGF-β1, Tβ R II and p27kipl in a panel of formalin-fixed and paraffin-embeded human specimens,including 49 extrahepatic bile duct carcinomas and 8 nomal common bile duct.The relationship between the expression and clinical pathology was analyzed.Results (1) In cholangiocarcinoma, the positive rates of TGF- β i, TβR II and p27kipl were 71.43%(35/49), 36.73%(18/49) and 40.82(20/49) respectively.The positive rates of the above three proteins in normal common bile duct tissues were 12.50%(l/8)> 100%(8/8) and 87.50(7/8) respectively. The positivity of TGF-β1 was much higher in cholangiocarcinoma than normal common bile duct (P<0.05) . From normal controls to cholangiocarcinoma,the expression of Tβ RII and p27klpl were decreased or absent.(2) Comparing with non-metastatic group and clinical stage I ~ II , the positivity of TGF-β1 wassignificantly higher in metastatic group and clinical stage III ~ IV, respectively. Meanwhile,changes of tissues p27klpl among all groups were in a reverse relatioship to those of TGF- β1. TPRII positivity of cholangiocarcinoma in clinical stage III ~ IV was significantly lower than stage I - II. (3) The co-expression of TGF- β 1 and Tβ RII was negatively related with clinical stage(P<0.05). (4) In cholangiocarcinoma, it was found that p27 klplexpression was positively associated with TβR-II expression (rs=0. 724,P<0.01). (5) Moreover, there was a significant relationship between the expression of p27klpl and the co-expression of TGF-β, and TβR II (P<0.01).Conclusions (1) The overexpression of TGF-β1 and reduced expression of TβR II and p27klpl expression could be helpful in predicting poor biological of cholangiocarcinoma.(2) The loss of TGF-β 1-induced growth inhibition in cholangiocarcinoma cells may be related with the negative expression of TβRII. (3) In cholangiocarcinoma, P27klpl may be regulated by the TGF-β , pathway. (4) The results indicate that abnormality of the TGF-β1 pathway and down-regulation of P27klpl expression may be involed in tumorgenesis and progression of cholangiocarcinoma.