儿童颅内肿瘤5种多药耐药蛋白表达特点及临床意义

Expressions and Clinical Values of Five Types of Multidrug Resistance Protein in Children with Intracranial Tumors

目的探讨肿瘤多药耐药蛋白P-糖蛋白(P-gp)、多药耐药相关蛋白1(MRP1)、肺耐药相关蛋白(LRP)、谷胱甘肽-S-转移酶(GST-π)及DNA拓扑异构酶Ⅱα(TopoⅡα)在儿童颅内肿瘤的表达特点,为其临床化疗方案的选择提供实验依据。方法分析本院2000年1月-2004年12月收治的临床资料完整、手术切除并经病理检查证实为儿童颅内肿瘤的石蜡标本38例,应用免疫组织化学S-P法检测38例颅内肿瘤儿童中多药耐药蛋白P-gp、MRP1、LRP、GST-π及TopoⅡα的表达;以10例非肿瘤患儿脑组织作为对照。结果1.颅内肿瘤患儿脑组织P-gp、GST-π、TopoⅡα、MRP1和LRP阳性表达率分别为65.8%、60.5%、47.4%、44.7%和44.7%,非肿瘤患儿脑组织P-gp阳性表达率为10%,其他4种多药耐药蛋白均为阴性。二组阳性表达率有显著性差异(P<0.01)。2.同一病理类型5种多药耐药蛋白的表达及同一耐药蛋白在不同病理类型间的表达均无显著性差异(Pa>0.05)。3.P-gp在星形细胞瘤和髓母细胞瘤的血管内皮细胞表达较高,而在颅咽管瘤和室管膜瘤组织则不明显。P-gp、GST-π在低恶性组和高恶性组间表达比较均有显著性差异(Pa<0.05)。结论儿童颅内肿瘤化疗失败的主要原因与血脑脊液屏障、血肿瘤屏障对化疗药物阻滞及肿瘤细胞本身的原发耐药密切相关。不同儿童颅内肿瘤的耐药性有各自的特点,有助于临床个体化化疗方案的制订。如果针对性地阻断这些耐药相关因素,能提高儿童颅内肿瘤的化疗效果。

Objective To explore the expressions and clinical values of multidrug resistance protein, including P - glycoprotein （ P - gp）, muhidrug resistance - associated protein （ MRP1 ）, lung resistance - related protein （ LRP）, topoisomerase Ⅱα （ TopoⅡα ） and glutathione - S- transferase- π（ GST- π） ,which may provide clues for the choice of anticancer drug in chemotherapy schedule for the children with intracranial tumors. Methods Thirty - eight cases of paraffin samples from pediatric brain tumors were analyzed, with the integrity of clinical data, surgical resection and confirmed by pathological examination, who were admitted from Jan. 2000 to Dec. 2004 in children＇s Hospital Affiliated to Chongqing Medical University. The expressions of P - gp, MRP1 ,Topo Ⅱα, LRP and GST -π were detected in 38 intracranial tumor cases by Streptavidin- Peroxidase immunohistochemistry staining method,and 10 cases of brain tissue of traumatic brain injury were taken as controls. Results 1. Of all 38 cases, the positive expression rates of P - gp, GST - π, Topo Ⅱα, MRP1 and LRP were 65.8% , 60.5% , 47.4% ,44.7% and 44.7% ,respectively,and 10% positive expression of P- gp and no expressions of others were detected in controls. The expressions of the 5 proteins in 2 groups were different（P 〈 0.01 ）. 2. The expression rates of the 5 muhidrug resistance protein in the same pat-hological type had no differences, and the expressions of the same muhidrug resistance protein in the 4 intracranial tumors were no differences（Pa 〉 0.05 ）. 3. The high expression of P - gp was observed in the vascular endothelial cells of astrocytoma and medulloblastoma, and low expression was detected in craniopharyngioma and ependymocytoma. The different expressions of P - gp and GST - π were detected between the low and high malignant tumors （P 〈 0.05 ）. Conclusions The blockage to the chemotherapy drugs caused by blood -brain barrier and blood - tumor barrier and primary muhidrug resistance of the tumor cells were the main reasons for the failure of the chemotherapy on intracranial tumors in children. There are different muhidrug resistant agents detected in different intracranial tumors of children,and the curative effects of the chemotherapy will be improved markedly if the expression of the muhidrug resistance gene is blocked.