IDH 野生型胶质母细胞瘤的组织病理特征及分子病理特征分析

Analysis of histopathological features and molecular pathological features of IDH wild-type glioblastoma

目的研究异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤(GBM)的组织病理及分子病理特征。方法选取2021年9月—2023年8月于河北大学附属医院神经外科接受手术治疗的74例GBM患者为研究对象,采用苏木精-伊红染色观察组织病理学特点;采用免疫组织化学染色及二代测序方法研究分子病理学特征;采用Kaplan-Meier法绘制生存分析曲线,分析患者生存期与IDH1突变之间的关系。结果74例GBM患者中男性占60.81%(45/74),患者年龄为(55.23±4.58)岁。58例为额叶肿瘤,16例为颞叶肿瘤。苏木精-伊红染色组织形态学结果显示,82.43%(61/74)的肿瘤组织可见典型的栅栏状坏死、血管增生、肿瘤异型性显著,符合典型GBM组织形态特点,其余肿瘤组织形态学符合2级或3级星形细胞瘤的形态特征。免疫组织化学染色结果显示,所有肿瘤IDH1 R132H染色均为阴性,Ki-67染色示平均阳性率为38%。二代测序分子病理结果显示,所有组织IDH1/2均为阴性,表皮生长因子受体(EGFR)扩增阳性占74.32%(55/74),端粒酶逆转录酶(TERT)启动子区域突变占59.46%(44/74)。细胞周期素依赖性激酶抑制因子2A/B(CDKN2A/B)发生纯合性缺失的比例为33.78%(25/74)。O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子区甲基化水平高表达占47.30%(35/74)。结论GBM具有IDH野生型的分子特征,部分病例伴有EGFR扩增、TERT启动子区突变、CDKN2A/B纯和缺失、MGMT启动子区高甲基化的分子改变。

Objective To explore the histopathological and molecular pathological features of isocitrate dehydrogenase(IDH)wild-type glioblastoma(GBM).Methods From September 2021 to August 2023,74 GBM patients with surgery at the Department of Neurosurgery,Affiliated Hospital of Hebei University were selected as the study subject.Hematoxylin-eosin staining was used to observe the pathological characteristics of tissues.Immunohistochemical staining and next-generation sequencing were used to analyze molecular pathological features.Kaplan-Meier method was used to plot survival analysis curves to analyze the relationship between patient survival and IDH1 mutations.Results Among 74 cases of GBM,males accounted for 60.81%(45/74),and the age was(55.23±4.58)years old.Fifty-eight cases of tumors were located in the frontal lobe and 16 cases were located in the temporal lobe.The histological results of hematoxylin-eosin staining showed that 82.43%(61/74)of tumor tissues showed typical palisade necrosis,vascular proliferation,and significant tumor atypia,consistent with the typical GBM tissue morphological characteristics.The morphology of other tumor tissues matched the morphological characteristics of grade 2 or 3 astrocytoma.Immunohistochemical staining showed that all tumors were negative for IDH1 R132H staining,while Ki-67 staining showed an average positive rate of 38%.Results of the next-generation sequencing molecular pathology showed that all tissues were negative for IDH1/2,with positive amplification of epidermal growth factor receptor(EGFR)accounting for 74.32%(55/74)and telomerase reverse transcriptase(TERT)promoter region mutations accounting for 59.46%(44/74).The proportion of pure deletion of cyclin dependent kinase inhibitor 2A/B(CDKN2A/B)was 33.78%(25/74).The high expression level of methylation in the promoter region of O6-methylguanine-DNA methyltransferase(MGMT)accounted for 47.30%(35/74).Conclusions GBM exhibits molecular features of IDH wild-type,with some cases accompanied by EGFR amplification,TERT promoter region mutations,CDKN2A/B homozygous deletion,and MGMT promoter region hypermethylation.