P-GLYCOPROTEIN EXPRESSION AS A PREDICTOR OF THE OUTCOME OF THERAPY FOR NEUROBLASTOMA
P-GLYCOPROTEIN EXPRESSION AS A PREDICTOR OF THE OUTCOME OF THERAPY FOR NEUROBLASTOMA
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DOI：
10.1056/nejm199112053252304
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发表时间：
1991-12-05
影响因子：
158.5
通讯作者：
LING, V
中科院分区：
文献类型：
--
作者：
CHAN, HSL;HADDAD, G;LING, V
背景和方法。肿瘤化疗中的多药耐药以P-糖蛋白基因表达增加为特征，P-糖蛋白作为ATP依赖性药物外排泵。为了确定P-糖蛋白水平是否具有预后价值，我们对67例神经母细胞瘤患儿的连续肿瘤样本进行了回顾性研究，用化学方法测定了这些水平。在2例I期疾病患者、21例II期疾病患者或8例IVS期疾病患者的治疗前样本中均未检测到P-糖蛋白，但在17例III期疾病患者中的1例（6%）和19例IV期疾病患者中的12例（63%）的样本中检测到P-糖蛋白。在44例非局限性神经母细胞瘤（III期、IVS期或IV期）患者中，31例P-糖蛋白阴性患者中有26例对初步治疗完全缓解，而13例P-糖蛋白阳性患者中有6例完全缓解（84% vs. 46%，Fisher精确检验P = 0.0232）。结果的对数秩分析，同时根据肿瘤分期和年龄分层，显示P-糖蛋白阴性组的无复发生存期（P = 0.0011）和总生存期（P = 0.0373）明显长于阳性组。治疗前P-糖蛋白的表达可预测非局限性神经母细胞瘤治疗的成败。神经母细胞瘤可能是一个有前途的肿瘤治疗与抗癌药物治疗结合化疗增敏剂能够逆转P-糖蛋白介导的多药耐药。
Background and Methods. Multidrug resistance in chemotherapy for cancer is characterized by increased genetic expression of P-glycoprotein, which acts as an ATP-dependent drug-efflux pump. To determine whether P-glycoprotein levels are of prognostic value in such cases, we measured these levels immunohistochemically in a retrospective study of sequential tumor samples from 67 children with neuroblastoma.Results. P-glycoprotein was not detected in pretreatment samples from either of the 2 patients with Stage I disease, any of the 21 with Stage II disease, or any of the 8 with Stage IVS disease, but it was detected in the samples from 1 of the 17 patients with Stage III disease (6 percent) and 12 of the 19 with Stage IV disease (63 percent). Of the 44 patients with nonlocalized neuroblastoma (Stage III, IVS, or IV), 26 of the 31 who were negative for P-glycoprotein had a complete response to primary treatment, as compared with 6 of the 13 who were positive for P-glycoprotein (84 percent vs. 46 percent, P = 0.0232 by Fisher's exact test). Log-rank analysis of outcome, with simultaneous stratification according to tumor stage and age, showed that the group that was negative for P-glycoprotein had significantly longer relapse-free survival (P = 0.0011) and overall survival (P = 0.0373) than the group that was positive.Conclusions. Expression of P-glycoprotein before treatment may predict the success or failure of therapy for nonlocalized neuroblastoma. Neuroblastoma may be a promising tumor to treat with anticancer drug therapy combined with a chemosensitizing agent capable of reversing P-glycoprotein-mediated multidrug resistance.