视网膜母细胞瘤多药耐药相关蛋白的研究

摘要

Objective To detect the expression of P-glycoprotein (P-gp), lung resistance associated protein (LRP) and muhidrug resistance associated protein (MRP) in retinoblastoma (Rb), to analyze the relationship between the expression of multidrug resistant (MDR) markers with clinic. pathological factors, the correlations among these three markers, and to study the possible mechanism of multidrug resistance in Rb. Methods It was an experimental study. Seventy-five cases of Rb were studied with immunohistechemical methods using antibodies against P-gp, LRP and MRP. The relationship betweer their expression and the clinicopathological features of Rb, and the relationship between the expression of these three markers were investigated. Results The positive expression rates of P-gp, LRP and MRP were 64.0%, 25.3%, 36.0% in R.b, respectively. The co-expression rates of P-gp and LRP, P-gp and MRP, LRP and MRP were 18.7%, 32.0%, 20.0%, respectively. All tested proteins showed significan correlation to the differentiation of the tumor (P = 0.006, 0.000, 0.000, respectively), but no correlatior was found between the expression of these markers and the age or sex of the patients. Significant positive correlations were observed between P-gp and MRP expression (P = 0.001), and between LRP and MRP expression (P = 0.000). Conclusions The intrinsic multidrug resistance of Rb involves the combined effects of P-gp, LRP and M R P.%目的 检测P-糖蛋白(P-Gp)、多药耐药基因相关蛋白(MRP)及肺耐药相关蛋白(LRP)在视网膜母细胞瘤(Rb)中的表达及临床意义;初步分析Rb患者临床病理指标与MRP间的关系;探讨Rb多药耐药现象的可能机制.方法 实验研究.应用免疫组织化学染色方法检测P-gp、MRP、LRP在75例Rb肿瘤标本中的表达情况.分析3种蛋白表达的相关性及其与患者年龄、性别、眼别、临床表现、组织病理分化程度等临床病理指标的相关性.各蛋白表达情况与一般临床特点、组织病理学特征的比较采用卡方检验,各蛋白间的相关性采用多元相关分析.结果 P-Gp、LRP、MRP蛋自在Rb中阳性表达率分别为64.0%、25.3%、36.0%.P-gp与LRP、P-gp与MRP、LRP与MRP的共表达阳性率分别为18.7%、32.0%、20.0%.P-gp、LRP、MRP在分化型Rb组织中的阳性表达率均高于杀分化型,且组间差异具有统计学意义(χ2=8.002,χ2=17.327,χ2=28.421;P<0.05).3种蛋白的表达均与年龄、性别、眼别无关(χ2=0.003～3.385,P>0.05).P-gp、LRP的表达分别与MRP的表达其有相关性(r=0.389,r=0.521;P<0.05).结论 Rb原发性多药耐药的形成是一个多因素、多步弱的复杂过程,与包括P-gp、LRP、MRP等在内的多项因素的参与有关.P-gp、LRP、MRP蛋白可以作为反映Rb耐药的分子基础,耐药相关标志的联合检测更有利于准确判断Rb的多药耐药状态,为Rb化学治疗提供科学的理论依据.