Frat与β-连环素在肺癌中的表达及与临床病理因素的关系

Expressions of Frat andβ-catenin in lung cancer and their clinicopathological correlations

背景与目的Frat(frequently rearranged in advanced T-cell lymphomas)是Wnt(wingless/int)信号传导途径的正向调节因子,通过结合糖原合成酶激酶3(glycogen synthase kinase,GSK3),抑制GSK3依赖的磷酸化作用,从而阻止β-连环素(β-catenin)的降解,β-catenin通过与TCFs(T cell factors)结合而激活靶基因。本研究的目的是探讨Frat和β-catenin在肺癌中的表达及其与各临床病理因素的关系。方法采用组织芯片和免疫组织化学法检测52例肺癌标本中Frat和β-catenin的表达。结果Frat的阳性表达率为75.00%,其中高分化,中分化和低分化非小细胞肺癌(non-small cell lung cancer,NSCLC)中Frat的阳性率分别为41.67%(5/ 12),83.33%(15/18)和88.24%(15/17),差异有统计学意义(x^2=9.229,P=0.01)。β-catenin的细胞表达异常率为71.15%,高分化,中分化和低分化NSCLC中β-catenin的表达异常率分别为41.67%(5/12),61.11%(11/18)和100%(17/17),差异有统计学意义(x^2=12.601,P=0.002)。结论β-catenin的细胞表达异常与NSCLC的低分化正相关,Frat的表达与NSCLC的低分化和β-catenin的表达异常正相关。

Background and objective Frat proteins are positive regulator of Wnt-signal transduction.By binding to GSK3,Frat prevents the phosphorylation and concomitant degradation of β-catenin and allows the activation of downstream targetgenes by β-catenin/TCF complexes. The aim of this study is to investigate the protein ex- pression of Frat and β-catenin and their clinicopathological correlations in lung cancer. Methods By means of tissue chip technique and immunohistochemical method, 52 cases of lung carcinoma were examed to detect the expression of Frat and β-catenin. Results The positive expression rate of Frat was 75% . The positive expression rate of Frat in well,moderately and poorly differentiated NSCLCs were 41.67%（5/12）, 83.33%（15/18） and 88.24%（15/17）. There was a significant difference in Frat expression among well,moderately and poorly differentiated NSCLCs （X^2= 9.229, P=0.01）. The abnormal cell expression rate of β-catenin was 71.15%. The abnormal cell expression rate of β-catenin in well,moderately and poorly differentiated NSCLCs were 41.67%（5/12）, 61.11%（11/18） and 100%（17/ 17）. There was a significant difference （X^2=12.601, P=0.002）. Conclusion The abnormal cell expression of β- catenin is associated with pooly differentiated NSCLCs. The expression of Frat is positively correlated with the degree of tumor differentiation and the abnormal cell expression of β-catenin.