分子病理与组织病理对胶质瘤诊断的一致性分析
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摘要
目的探究胶质瘤分子病理与组织病理结果的一致性及分子病理对胶质瘤组织病理诊断的修正作用。方法回顾分析2017年1月-2018年5月解放军总医院第一医学中心神经外科手术治疗的89例胶质瘤患者(低级别胶质瘤25例,高级别胶质瘤64例)的分子病理及组织病理结果,对相应指标进行诊断一致性分析。结果分子病理与组织病理在胶质瘤级别的诊断一致率为79.8%,在判定IDH-1突变、MGMT甲基化、ATRX突变时,组织病理与分子病理的诊断一致率分别为93.3%、57.3%、79.8%,分子病理对组织病理的以上三项检测指标的诊断修正率分别为6.7%、42.7%、20.2%。低级别胶质瘤组与高级别胶质瘤组相比,只在用两种方法检测MGMT甲基化时出现诊断一致率的差异(76.0%vs 50.0%,P=0.026);而在检测综合病理诊断类型、IDH-1突变、ATRX突变方面,两组诊断一致率无差异。结论组织病理与分子病理对胶质瘤的诊断一致率在IDH-1突变方面较高;而在胶质瘤类型的综合诊断、MGMT甲基化的诊断、ATRX突变的诊断方面,分子病理更为准确。
Objective To explore the consistency of results of molecular pathology and histopathology in patients with glioma and the role of molecular pathology in improving the accuracy of pathological diagnosis in glioma. Methods Eighty-nine patients with glioma(25 low-grade gliomas, 64 high-grade gliomas) were treated in neurosurgery department of the First Medical Center of Chinese PLA General Hospital from January 2017 to May 2018, and their molecular pathological and histopathological results were retrospectively analyzed. Then diagnostic consistency of the corresponding indicators between two groups was investigated.Patients with gliomas were divided into high-grade glioma group and low-grade glioma group, and the molecular and pathological diagnosis consistency rates of the two groups were statistically analyzed. Results The consistency rate of molecular pathology and histopathology in diagnosis of glioma grade was 79.8%. The diagnostic agreement rates of histopathology and molecular pathology were 93.3% and 57.3%, 79.8%, respectively. In terms of judging IDH-1 mutation, MGMT methylation and ATRX mutation, the accuracy were improved by 6.7%, 42.7%, and 20.2%, respectively. There was signi?cant difference in the diagnostic agreement rate of MGMT methylation between high-grade glioma group and low-grade glioma group(76.0% vs 50.0%, P=0.026), but no difference in comprehensive pathological diagnosis type, IDH-1 mutation, ATRX mutation. Conclusion The diagnostic agreement rate of histopathology and molecular pathology is higher for IDH-1 mutation of glioma. While molecular pathology is more accurate in the comprehensive diagnosis of glioma grade, the diagnosis of MGMT methylation and ATRX mutations.
Objective To explore the consistency of results of molecular pathology and histopathology in patients with glioma and the role of molecular pathology in improving the accuracy of pathological diagnosis in glioma. Methods Eighty-nine patients with glioma(25 low-grade gliomas, 64 high-grade gliomas) were treated in neurosurgery department of the First Medical Center of Chinese PLA General Hospital from January 2017 to May 2018, and their molecular pathological and histopathological results were retrospectively analyzed. Then diagnostic consistency of the corresponding indicators between two groups was investigated.Patients with gliomas were divided into high-grade glioma group and low-grade glioma group, and the molecular and pathological diagnosis consistency rates of the two groups were statistically analyzed. Results The consistency rate of molecular pathology and histopathology in diagnosis of glioma grade was 79.8%. The diagnostic agreement rates of histopathology and molecular pathology were 93.3% and 57.3%, 79.8%, respectively. In terms of judging IDH-1 mutation, MGMT methylation and ATRX mutation, the accuracy were improved by 6.7%, 42.7%, and 20.2%, respectively. There was signi?cant difference in the diagnostic agreement rate of MGMT methylation between high-grade glioma group and low-grade glioma group(76.0% vs 50.0%, P=0.026), but no difference in comprehensive pathological diagnosis type, IDH-1 mutation, ATRX mutation. Conclusion The diagnostic agreement rate of histopathology and molecular pathology is higher for IDH-1 mutation of glioma. While molecular pathology is more accurate in the comprehensive diagnosis of glioma grade, the diagnosis of MGMT methylation and ATRX mutations.
引文
1 Louis DN,Ohgaki H,Wiestler OD,et al.The 2007 WHOclassification of tumours of the central nervous system[J].Acta Neuropathol,2007,114(2):97-109.
2 Louis DN.The next step in brain tumor classification:"Let us now praise famous men"...or molecules?[J].Acta Neuropathol,2012,124(6):761-762.
3 Komori T.The 2016 WHO Classification of Tumours of the Central Nervous System:The Major Points of Revision[J].Neurol Med Chir(Tokyo),2017,57(7):301-311.
4 Neuropathology Group of Pathology Branch of the Chinese Medical Association.World Health Organization classification of tumours of the central nervous system:a summary[J].Zhonghua Bing Li Xue Za Zhi,2016,45(11):745-747.
5 Ballester LY,Huse JT,Tang G,et al.Molecular classification of adult diffuse gliomas:conflicting IDH1/IDH2,ATRX,and 1p/19q results[J].Hum Pathol,2017,69:15-22.
6杜伟,陈义兵,魏新亭.2016版《WHO中枢神经系统肿瘤分类》更新解读[J].中华神经外科杂志,2016,32(11):1095-1098.
7郑长青,季守平,宫锋,等.MGMT基因启动子甲基化检测在脑胶质瘤化疗中的意义[J].癌症:英文版,2009,28(6):575-580.
8赵健,雷建宾,姜海涛,等.MGMT在人脑胶质瘤中的表达及其意义[J].现代肿瘤医学,2008,16(1):26-29.
9中华医学会病理学分会脑神经病理学组.2016 WHO中枢神经系统肿瘤分类第4版修订版概述及胶质瘤部分介绍[J].中华病理学杂志,2016,45(11):745-747.
10 Back M,Rodriguez M,Jayamanne D,et al.Understanding the Revised Fourth Edition of the World Health Organization Classification of Tumours of the Central Nervous System(2016)for Clinical Decision-making:A Guide for Oncologists Managing Patients with Glioma[J].Clin Oncol(R Coll Radiol),2018,30(9):556-562.
11徐影,刘畅.染色体1p/19q缺失与P53、IDH1突变蛋白在少突胶质细胞肿瘤中的表达及相关性[J].哈尔滨医科大学学报,2015,49(3):204-208.
12 Mellai M,Annovazzi L,Senetta R,et al.Diagnostic revision of 206adult gliomas(including 40 oligoastrocytomas)based on ATRX,IDH1/2 and 1p/19q status[J].J Neurooncol,2017,131(2):213-222.
13李朝晖,郭志钢,李庆伟.弥漫性较低级别胶质瘤的整合性分子病理分型研究进展[J].中国肿瘤临床,2016,43(12):541-544.
14 Reuss DE,Sahm F,Schrimpf D,et al.ATRX and IDH1-R132Himmunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an"integrated"diagnostic approach for adult astrocytoma,oligodendroglioma and glioblastoma[J].Acta Neuropathol,2015,129(1):133-146.
15 Polivka J,Jr.,Polivka J,Repik T,et al.Co-deletion of 1p/19q as Prognostic and Predictive Biomarker for Patients in West Bohemia with Anaplastic Oligodendroglioma[J].Anticancer Res,2016,36(1):471-476.
16罗秀萍,陈茂君,杨前美,等.不同病理类型及分级胶质瘤细胞IDH1基因突变临床研究[J].陕西医学杂志,2016,45(7):912-914.
17 Millward CP,Brodbelt AR,Haylock B,et al.The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy[J].Acta Neurochir(Wien),2016,158(10):1943-1953.
18 Lee A,Youssef I,Osborn VW,et al.The utilization of MGMTpromoter methylation testing in United States hospitals for glioblastoma and its impact on prognosis[J].J Clin Neurosci,2018,51:85-90.
19蒋梦婉,刘琪,李嘉瑶,等.异柠檬酸脱氢酶-1突变及MGMT甲基化在脑胶质瘤的诊断及治疗研究进展[J].现代生物医学进展,2016,16(5):970-973.
20吴会芳,顾斌,张敏,等.ATRX和P53蛋白在弥漫性胶质瘤中的表达及意义[J].中国实用医刊,2018,45(16):1-3.
21 Modrek AS,Golub D,Khan T,et al.Low-Grade Astrocytoma Mutations in IDH1,P53,and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2[J].Cell Rep,2017,21(5):1267-1280.
22李卓,朴月善,张立彦,等.ATRX在胶质瘤诊断及患者预后评估中的应用[J].中华病理学杂志,2017,46(10):690-694.
23徐维林,王强,张宏伟,等.长周期替莫唑胺治疗高级别胶质瘤生存期观察[J].解放军医学院学报,2016,37(7):725-727.
24朱巍,崔萌,马晓东.岛叶低级别胶质瘤的生物学特性及预后评估[J].解放军医学院学报,2018,39(1):5-8.
2 Louis DN.The next step in brain tumor classification:"Let us now praise famous men"...or molecules?[J].Acta Neuropathol,2012,124(6):761-762.
3 Komori T.The 2016 WHO Classification of Tumours of the Central Nervous System:The Major Points of Revision[J].Neurol Med Chir(Tokyo),2017,57(7):301-311.
4 Neuropathology Group of Pathology Branch of the Chinese Medical Association.World Health Organization classification of tumours of the central nervous system:a summary[J].Zhonghua Bing Li Xue Za Zhi,2016,45(11):745-747.
5 Ballester LY,Huse JT,Tang G,et al.Molecular classification of adult diffuse gliomas:conflicting IDH1/IDH2,ATRX,and 1p/19q results[J].Hum Pathol,2017,69:15-22.
6杜伟,陈义兵,魏新亭.2016版《WHO中枢神经系统肿瘤分类》更新解读[J].中华神经外科杂志,2016,32(11):1095-1098.
7郑长青,季守平,宫锋,等.MGMT基因启动子甲基化检测在脑胶质瘤化疗中的意义[J].癌症:英文版,2009,28(6):575-580.
8赵健,雷建宾,姜海涛,等.MGMT在人脑胶质瘤中的表达及其意义[J].现代肿瘤医学,2008,16(1):26-29.
9中华医学会病理学分会脑神经病理学组.2016 WHO中枢神经系统肿瘤分类第4版修订版概述及胶质瘤部分介绍[J].中华病理学杂志,2016,45(11):745-747.
10 Back M,Rodriguez M,Jayamanne D,et al.Understanding the Revised Fourth Edition of the World Health Organization Classification of Tumours of the Central Nervous System(2016)for Clinical Decision-making:A Guide for Oncologists Managing Patients with Glioma[J].Clin Oncol(R Coll Radiol),2018,30(9):556-562.
11徐影,刘畅.染色体1p/19q缺失与P53、IDH1突变蛋白在少突胶质细胞肿瘤中的表达及相关性[J].哈尔滨医科大学学报,2015,49(3):204-208.
12 Mellai M,Annovazzi L,Senetta R,et al.Diagnostic revision of 206adult gliomas(including 40 oligoastrocytomas)based on ATRX,IDH1/2 and 1p/19q status[J].J Neurooncol,2017,131(2):213-222.
13李朝晖,郭志钢,李庆伟.弥漫性较低级别胶质瘤的整合性分子病理分型研究进展[J].中国肿瘤临床,2016,43(12):541-544.
14 Reuss DE,Sahm F,Schrimpf D,et al.ATRX and IDH1-R132Himmunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an"integrated"diagnostic approach for adult astrocytoma,oligodendroglioma and glioblastoma[J].Acta Neuropathol,2015,129(1):133-146.
15 Polivka J,Jr.,Polivka J,Repik T,et al.Co-deletion of 1p/19q as Prognostic and Predictive Biomarker for Patients in West Bohemia with Anaplastic Oligodendroglioma[J].Anticancer Res,2016,36(1):471-476.
16罗秀萍,陈茂君,杨前美,等.不同病理类型及分级胶质瘤细胞IDH1基因突变临床研究[J].陕西医学杂志,2016,45(7):912-914.
17 Millward CP,Brodbelt AR,Haylock B,et al.The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy[J].Acta Neurochir(Wien),2016,158(10):1943-1953.
18 Lee A,Youssef I,Osborn VW,et al.The utilization of MGMTpromoter methylation testing in United States hospitals for glioblastoma and its impact on prognosis[J].J Clin Neurosci,2018,51:85-90.
19蒋梦婉,刘琪,李嘉瑶,等.异柠檬酸脱氢酶-1突变及MGMT甲基化在脑胶质瘤的诊断及治疗研究进展[J].现代生物医学进展,2016,16(5):970-973.
20吴会芳,顾斌,张敏,等.ATRX和P53蛋白在弥漫性胶质瘤中的表达及意义[J].中国实用医刊,2018,45(16):1-3.
21 Modrek AS,Golub D,Khan T,et al.Low-Grade Astrocytoma Mutations in IDH1,P53,and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2[J].Cell Rep,2017,21(5):1267-1280.
22李卓,朴月善,张立彦,等.ATRX在胶质瘤诊断及患者预后评估中的应用[J].中华病理学杂志,2017,46(10):690-694.
23徐维林,王强,张宏伟,等.长周期替莫唑胺治疗高级别胶质瘤生存期观察[J].解放军医学院学报,2016,37(7):725-727.
24朱巍,崔萌,马晓东.岛叶低级别胶质瘤的生物学特性及预后评估[J].解放军医学院学报,2018,39(1):5-8.
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