摘要目的 研究Hedgehog(Hh)信号通路相关蛋白(Gli 1,Ptch-1和Shh)在肝内胆管细胞癌(intrahepatic cholangio carcinoma,ICC)中的表达及意义.通过对ICC和癌旁组织中Hh通路相关蛋白(Gli 1、Ptch-1和Shh)的表达进行检测,探讨其与ICC临床病理特征之间的关系及意义.方法 免疫组化法对43例ICC组织及癌旁组织进行Gli 1、Ptch-1和Shh蛋白的检测;Real-time RT-PCR检测12例ICC组织和癌旁组织中mRNA的表达,并与患者临床病理特征进行相关性分析.结果 43例ICC组织中,Gli 1、Ptch-1和Shh阳性表达率分别为74.4%(32/43)、69.8% (30/43),和62.8%(27/43),与癌旁组织表达比较差异具有统计学意义(P值分别为0.003、0.006和0.008);三者的表达与肿瘤的大小有关(P值分别为0.039、0.044和0.047);三者的表达与肿瘤的分化程度相关(P值分别为0.026,0.039和0.049);三者的表达与淋巴结转移具有相关性(P均<0.05).Real-time PCR结果显示,12例ICC组织中均有Gli 1、Ptch-1和Shh的表达,且基因表达水平均高于癌旁正常组织(P均=0.001).结论 Hedgehog信号通路的相关蛋白在ICC组织中高表达,其异常激活可能与肝内胆管细胞癌发生密切相关.Gli 1、Ptch-1和Shh的表达可能与肿瘤的生长和转移密切相关.

abstractsObjective To study the expression of proteins associated with Hedgehog pathway in intrahepatic cholangiocarcinoma(ICC).Methods We detected the mRNA expression of Gli,Ptch-1,and Shh in 43 formalin-fixed,paraffin-embedded ICC tissues and tumor-adjacent tissues using immunohistochemistry.The mRNA expression of Gli1,Ptch-1,and Shh in 12 fresh ICC and tumor-adjacent tissues was also studied by RT-PCR.The relationship between Gli1,Ptch-1,and Shh expression and the clinical and pathological characteristics of ICC were investigated.Results Immunohistochemistry showed that Gli1,Ptch-1,and Shh were detected in 74.4%(32/43),69.8% (30/43),and 62.8% (27/43) of ICC cases,respectively.The expression level of all three proteins was higher in ICC than that in tumor-adjacent tissues (P=0.003,0.006,0.008).The expression of Gli 1,Ptch-1,and Shh was significantly correlated with the tumor size (P=0.039,0.044,0.047),pathological grade(P=0.026,0.039,0.049),and the tumor metastasis (P<0.05).Real-time PCR showed that the expression of Gli1,Ptch-1,and Shh was higher in ICC than that in tumor-adjacent tissues (P=0.001).Conclusion Our findings strongly suggest that the expression of Gli-1,Shh,and Ptch-1 in the Hedgehog signaling pathway was elevated in ICC,indicating that the abnormal activation of Hh signaling pathway plays roles in ICC.Gli 1,Ptch-1,and Shh expression may be closely related to ICC growth and invasion.