乳腺癌中 Hedgehog 信号通路的表达及其与 LKB1 基因相关性的研究

摘要

Objective:To investigate the correlation between the expression of Hedgehog(Hh) signaling pathway members and gene LKBl in human breast carcinoma and the relationship of Hh signaling pathway members'expression with clinicopathological factors and prognosis. Methods: The expression of Hh signaling pathway members (including protein Shh,Smo,Sufu,Glil and Ptch ) and gene LKBl in 75 cases of breast cancer was assessed by immunohis-tochemistry,and their correlation was statistically analyzed,at the same time analyze the relationship of Hh signaling pathway members's expression with clinicopathological factors and prognosis. Results; In the 75 breast cancer samples,69(92. 0% ) ,58(77.3% ) ,65(86.7% ) ,50(66. 7% ) ,34(45. 3% )and 33(44. 0% ) highly expressed protein Shh,Glil ,Smo,Ptch,Sufu and LKBl respectively. The expression of Hh signaling pathway and gene LKBl had negative correlation and this correlation had statistical significance; Hh signaling pathway is activated in human breast cancer which is not related to size of carcinomor, may be related to age, molecular subtypes and lymphoid node me-tabasis; and the prognosis of patients whose Hh signaling pathway expressed highly is not good. Conclusion; Hedgehog signaling pathway members are expressed highly in breast cancer, and its expression had negative correlation with the expression of gene LKBl ,the relationship between them may make important influence in the diagnosis, treatment and prognosis of breast cancer.%目的:探讨Hedgehog (Hh)信号通路主要蛋白在乳腺癌中的表达及其与LKB1基因的相关性,以及与临床病理特征、预后的关系.方法:采用免疫组化方法检测75例人乳腺癌标本中Hh信号通路主要蛋白( Shh、Smo、Sufu、Gli1、Ptch)及LKB1基因的表达,分析二者相关性,并分析Hh信号通路的表达与临床病理特征及预后的关系.结果:在75例乳腺癌样本中,阳性表达Shh、Gli1、Smo、Ptch、Sufu、LKB1分别为69(92.0％)、58(77.3％)、65(86.7％)、50( 66.7％)、34(45.3％)、33 (44.0％),而在其相邻的正常乳腺上皮不表达或低表达.Hh信号通路与LKB1的表达呈负相关；Hh信号通路的表达情况与患者年龄、淋巴结转移情况、分子分型具有一定的相关性,且高表达的患者预后较差.结论:Hh信号通路在乳腺癌中过度激活,与临床病理特征及预后相关,并与LKB1基因的表达呈负相关,两者之间的相互作用对乳腺癌的诊治及预后可能有重要影响.