论著 Original Article

免疫组织化学标记在儿童髓母细胞瘤分子分型中的应用及其临床意义

Published at: 2017年第37卷第1期

江贤萍 1 , 徐金永 1 , 陈乾 2 , 张欢 1 , 缪秋玲 1 , 宋建明 1
1 深圳市儿童医院病理科,广东 深圳 518038
2 深圳市儿童医院神经外科,广东 深圳 518038
通讯作者 建明 宋 Email: jamie898@163.com
DOI: 10.3978/j.issn.2095-6959.2017.01.015
基金:
深圳市科技创新委基础研究项目 JCYJ20140416141331501,JCYJ20150403100317076

摘要

目的:探讨免疫组织化学标记在儿童髓母细胞瘤分子分型中应用的可行性,分析分子分型相关蛋白的表达与肿瘤临床病理特点及预后的关系。方法:应用组织芯片技术及免疫组织化学Elivision法检测β-catenin,Gli-1,NPR3及KCNA1在40例儿童髓母细胞瘤中的表达,分析根据表达结果行分子分型的可行性及蛋白表达与年龄、性别、肿瘤部位、病理分型及预后的关系。结果:40例肿瘤组织中β-catenin,Gli-1,NPR3及KCNA1的阳性率分别为10%,55%,50%及30%,Gli-1阳性表达与患儿年龄及病理类型相关(P>0.05)。Kaplan-Meier生存分析提示<3岁年龄组及Gli-1阳性组患儿预后较差(P<0.05)。Cox比例风险回归分析显示患儿年龄、病理分型、Gli-1蛋白及NPR3蛋白表达是儿童髓母细胞瘤的独立预后因子(P<0.05)。22例髓母细胞瘤(medulloblastoma,MB)行分子分型,其中WNT型4例,SHH型10例,3型6例,4型2例,Kaplan-Meier生存分析提示分子分型与预后无关(P>0.05)。结论:β-catenin核阳或核浆阳可作为WNT型髓母细胞瘤的蛋白标志物,Gli-1表达与患儿年龄及病理学类型密切相关,阳性表达提示患儿预后较差,是独立的预后因子之一,但其表达与NPR3及KCNA1的表达有部分重叠,因此尚需结合SHH型、3型及4型髓母细胞瘤的其它分子检测方法进行准确的分子分型。


Application and clinical significance of immunohistochemical markers in molecular classification of pediatric medulloblastoma

Abstract

Objective: To explore the feasibility of immunohistochemical markers in molecular classification of pediatric medulloblastoma and to analyze the correlation of protein expression with clinicopathological characteristics and prognosis. Methods: Elivision immunohistochemistry was used to detect the expression of β-catenin, Gli-1, NPR3 and KCNA1 protein in tissue microarray containing 40 paraffin embedded pediatric medulloblastoma specimens. Chi-square test and Fisher exact test was used to analyze the correlation of expression with gender, age, tumor location and pathological subtypes. Follow-up data was handled by using Kaplan-Meier survival analysis, Log-Rank test and Cox regression analysis. Results: Positive expression ratio of β-catenin, Gli-1, NPR3 and KCNA1 protein were 10%, 55%, 50% and 30%. The positive expression of Gli-1 was correlated with the age of the children and the pathological type (P>0.05). Kaplan-Meier survival analysis showed that the prognosis of patients with <3 years of age group and the Gli-1 positive group was poor (P<0.05). Cox proportional hazard regression analysis showed that the age, pathologic type, the expression of Gli-1 and NPR3 protein were independent prognostic factors in children with medulloblastoma (P<0.05). There were 4 cases of type WNT, 10 cases of type SHH, 6 cases of type 3, 2 cases of type 4. Kaplan-Meier survival analysis suggested that molecular subgroup was not associated with prognosis (P>0.05). Conclusion: Positive expression of β-catenin in nuclear or nuclear and cytoplasm can be used as a protein marker of WNT type. The expression of Gli-1 is closely related to the age of the children and the pathological types, the positive expression suggests that the prognosis was poor, and it was one of the independent prognostic factors in pediatric medulloblastoma. Accurate subgrouping needs to be combined with other molecular detection methods because there is partial overlap in expression of Gli-1 with NPR3 and KCNA1 protein.


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引用

引用本文: 贤萍 江, 金永 徐, 乾 陈, 欢 张, 秋玲 缪, 建明 宋. 免疫组织化学标记在儿童髓母细胞瘤分子分型中的应用及其临床意义[J]. 临床与病理杂志, 2017, 37(1): 79-85.
Cite this article as: JIANG Xianping, XU Jinyong, CHEN Qian, ZHANG Huan, MIAO Qiuling, SONG Jianming . Application and clinical significance of immunohistochemical markers in molecular classification of pediatric medulloblastoma[J]. Journal of Clinical and Pathological Research, 2017, 37(1): 79-85.