非小细胞肺癌Bmi-1、p16^(INK4a)、p14^(ARF)蛋白表达关系研究

The Bmi-1 oncoprotein overexpression in non-small cell lung cancer is correlated with INK4A-ARF locus downexpression

目的探讨非小细胞肺癌(NSCLC)Bmi-1、p16INK4a、p14ARF蛋白表达之间的关系。方法首先采用免疫组织化学S-P方法对123例NSCLC癌组织中p16INK4a和p14ARF蛋白的表达进行检测。然后,以p16INK4a和p14ARF蛋白表达共阴性和共阳性的NSCLC患者癌组织样本为研究对象,分别称为(p16+p14)阴性组和(p16+p14)阳性组,再采用免疫组织化学S-P方法对这些病例癌组织中Bmi-1蛋白的表达进行检测。结果123例NSCLC标本中p16INK4a、p14ARF表达阴性率分别为40.65%(50/123)和72.36%(89/123),两种蛋白表达阴性率差异有非常显著的意义(P<0.01);其中有39例p16INK4a、p14ARF蛋白表达共阴性,表达共阴性率高达31.71%(39/123);还有24例p16INK4a、p14ARF蛋白表达共阳性,表达共阳性率为19.51%(24/123)。(p16+p14)阴性组中有28例显示强阳性或阳性表达Bmi-1蛋白,阳性率达71.79%(28/39),其余11例显示弱阳性或阴性表达Bmi-1蛋白,仅占28.21%(11/39),两者差异有显著意义(P<0.05);(p16+p14)阳性组中有5例显示强阳性或阳性表达Bmi-1蛋白,阳性率仅为20.83%,其余19例显示弱阳性或阴性表达Bmi-1蛋白,占79.17%,两者差异有显著意义(P<0.05)。相关分析结果显示,本组NSCLC癌组织Bmi-1与p16INK4a、p14ARF蛋白表达相互之间有显著相关性(P<0.05)。结论NSCLC癌组织中p16INK4a、p14ARF蛋白表达有较高的阴性率,其原因与Bmi-1蛋白的过表达密切相关。

Objective To assess Bmi-1 expression in resectable non-small cell lung cancer（NSCLC） in association with p16INK4a and p14ARF（=human p19ARF）.Methods Sections were obtained from previous 10%-formalin-fixed and paraffin-embedded tissues.The protein expressions of p16INK4a and p14ARF were detected in 123 NSCLC samples by immunohistochemistry（S-P method） at first.Then the p16INK4a and p14ARF negative co-expression cases and positive co-expression cases were selected.These samples were divided into two groups,namely（p14＋p16） negative group and（p14＋p16） positive group,respectively.The protein expression of Bmi-1 was detected by immunohistochemistry.Results Negative expression of p16INK4a was detected in 50（40.65%） of 123 NSCLC cases.However,73 cases showed positive immunohistochemical result.Negative expression of p14ARF was detected in 89（72.36%） of 123 NSCLC cases.However,34 cases showed positive immunohistochemical result.The difference was significant for the negative rates of p16INK4a and p14ARF expressions（P0.01）.The p16INK4a and p14ARF negative co-expression cases and positive co-expression cases were 39 and 24,respectively.Tumors with moderate or strong Bmi-1 expression were more likely to have low levels of p16INK4a and p14ARF.Similarly,tumors negative for both,p16INK4a and p14ARF,exhibit moderate-strong Bmi-1 staining.Conclusion The inverse correlation of Bmi-1 and the INK4A-ARF locus protein expressions supports a possible role for Bmi-1 misregulation in lung carcinogenesis.