与小儿泌尿生殖系横纹肌肉瘤治疗相关的耐药基因研究

Characterization of multidrug resistance-related genes in pediatric genitourinary rhabdomyosarcoma

目的 分析小儿泌尿生殖系横纹肌肉瘤对化疗药物产生的多药耐药 (MDR)现象 ,及其对治疗效果的影响。方法 (1)用免疫组织化学的方法检测多药耐药基因 (MDR1)、多药耐药相关蛋白基因 (MRP)、肺耐药蛋白基因 (LRP)在 4 7例小儿泌尿生殖系横纹肌肉瘤病理组织中的蛋白表达 ,分别比较 3种耐药基因在横纹肌肉瘤患儿手术后 3年存活与死亡病例中的表达结果 ,以分析其与治疗效果的关系 ;(2 )用原位杂交 (ISH)的方法研究多药耐药基因 (MDR1)mRNA在小儿泌尿生殖系横纹肌肉瘤 5例复发病例新鲜肿瘤标本中的表达。 (3)做与RMS治疗相关多因素分析 ,了解MDR对治疗效果的影响。结果 (1)对 4 7例小儿泌尿生殖系横纹肌肉瘤做免疫组化检测 3种耐药基因 :MDR1阳性表达 2 1例 ,以阳性和强阳性表达为主 ,表达阴性组存活病例数多于表达阳性组 (χ2 检验 ,P <0 .0 0 5 ) ;MRP阳性表达 5例 ,以弱阳性为主 ,表达阴性组存活病例数与表达阳性组无差异 (χ2 检验 ,P >0 .0 5 ) ;LRP阳性表达 2 4例 ,以阳性和强阳性为主 ,表达阴性组存活病例数多于表达阳性组(χ2 检验 ,P <0 .0 0 5 )。 (2 )原位杂交检测 5例新鲜标本 ,4例有MDR1mRNA阳性表达。 (3)多因素分析证明MDR1及LRP与治疗效果相关。

Objective To analyse multidrug resistance(MDR) and its influence in the treatment of pediatric genitourinary rhabdomyosarcoma (RMS). Methods (1)To detect expression of multidrug resistance 1(MDR1)?multidrug resistance-associated protein (MRP) and lung resistance protein(LRP) by immunohistochemistry in 47 patients with genitourinary RMS. The survival numbers between positive and negative expression groups were compared. (2)In situ hybridization (ISH) was used to investigate mRNA expression of MDR1 in 5 fresh RMS specimens. (3) The factors related to 3 year postoperative survivals were analysed by using logistic regression. Results Immunohistochemistry examination was done in 47 RMS cases and 21 RMS had positive expression of MDR1. The survival numbers of negative expression group were higher than positive group(P< 0.005). There were only 5 RMS cases that had MRP positive expression. There was no significant difference between survival numbers of negative expression group and that of positive group(P> 0.05). 24 RMS had positive expression of LRP and survival numbers of negative expression group were also higher than that of positive group(P< 0.005). 4 had positive expression by ISH studies in 5 RMS. MDR1 and LRP were chosen by multivariate logistic regression. Conclusions MDR of pediatric genitourinary RMS could be detected by measuring the levels of protein and mRNA. High MDR1 and LRP expression were found in RMS and they had close relationship with the outcome of treatment. MRP expression was low and had no significant correlation with outcome.