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P-糖蛋白、多药耐药相关蛋白和谷胱苷肽S-转移酶在神经母细胞瘤中的表达及意义

Expression of glutathione S-transferase, P-glycoprotein, and multidrug resistance-associated protein in neuroblastoma and its clinical significance

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【作者】 吕庆杰李晓晗张锦华马颖王晓松姜卫国

【Author】 L Qingjie *, LI Xiaohan, ZHANG Jinhua, MA Ying, WANG Xiaosong, JIANG Weiguo. *Department of Pathology, No 2 Clinical College, China Medical University, Shenyang 110004, China

【机构】 中国医科大学第二临床学院病理科中国医科大学第二临床学院血液室中国医科大学第二临床学院病理科 110004沈阳110004沈阳

【摘要】 目的 探讨P 糖蛋白、多药耐药相关蛋白 (MRP)和谷胱苷肽S 转移酶 (GST π)在小儿神经母细胞瘤 (NB)中的表达及临床意义。方法 应用免疫组织化学SP法检测 70例NB组织中P 糖蛋白、MRP和GST π的表达。结果 P 糖蛋白、MRP和GST π的阳性率分别为 61 4% ( 43 / 70 )、3 8 6%( 2 7/ 70 )和 5 1 4% ( 3 6/ 70 )。P 糖蛋白与MRP、P 糖蛋白与GST π、MRP与GST π及P 糖蛋白、MRP与GST π共表达阳性率分别为 3 2 9% ( 2 3 / 70 )、3 5 7% ( 2 5 / 70 )、2 7 1% ( 19/ 70 )和 2 4 3 % ( 17/ 70 )。P 糖蛋白、GST π与MRP均具有相关性 (r =0 3 87,P =0 0 0 1;r=0 3 0 0 ,P =0 0 12 ) ,P 糖蛋白与GST π无相关性 (r=0 169,P =0 161)。年龄大于 1岁的NBP 糖蛋白和MRP的表达阳性率 ( 72 3 % ,48 9% )均高于小于 1岁者 ( 3 9 1% ,17 4% ,P <0 0 5 )。分化性NBP 糖蛋白、MRP和GST π表达 ( 93 3 %、86 7%和80 0 % )均明显高于无分化的NB( 5 2 7%、2 5 5 %和 43 6% ,P <0 0 5 )。有转移的NBMRP表达( 61 9% )高于无转移者 ( 2 8 6% ,P <0 0 5 )。P 糖蛋白、MRP和GST π表达与性别和分期无关。MRP阳性者中位生存期和 2年累计生存率 ( 2 0个月 ,48 9% )均较阴性者 ( 2 4个月 ,77 9% )下降 (P <0 0 5 )?

【Abstract】 Objective To detect expression of p-glycoprotein(P-gp), multidrug resistance-associated protein (MRP), and glutathione S-transferase (GST-π), and to evaluate its clinical significance in neuroblastoma (NB). Methods SP immunohistochemical technique was used to investigate expression of P-gp, MRP, and GST-π in 70 cases of NB. Results The frequency of expression of P-gp, MRP, and GST-π was 61.4%, 38.6%, and 51.4%, respectively. The coexpression rate of P-gp and MRP, P-gp and GST-π, MRP and GST-π, P-gp, MRP and GST-π was 32.9%, 35.7%, 27.1%, and 24.3%, respectively. Significant positive correlation was observed between P-gp and MRP expression (P=0.001), and between MRP and GST-π expression (P=0.012), but no correlation was found between P-gp and GST-π expression. The expression of P-gp and MRP was higher in tumors from patients over 1 year old compared with those less than 1 year old at diagnosis (P=0.01, 0.018, respectively). MRP expression was higher in tumors from the metastatic than the non metaststic groups (P=0.015). All tested proteins showed significant relationship to the differentiation of the tumor (P=0.006, 0.000, 0.019, respectively), but no correlation was found to the stage of NB or sex of the patients. MRP expression was significantly related to the reduction of both median survival time and the two-year cumulative survival (P=0.02). In contrast, P-gp and GST-π expression had no correlation with survival. Conclusions The intrinsic multidrug resistance of NB involves the combined effects of P-gp , MRP, and GST-π. MRP expression may be an important parameter in predicting the prognosis of patients with NB.

【基金】 国家自然科学基金资助项目 ( 39470 739)
  • 【文献出处】 中华病理学杂志 ,Chinese Journal of Pathology , 编辑部邮箱 ,2002年06期
  • 【分类号】R739.4
  • 【被引频次】6
  • 【下载频次】101
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