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
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河北省自然科学基金项目 (H2022201008);河北省研究生创新资助项目 (CXZZBS2023001)


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

    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。

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    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.

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刘国鸣,肖梦麟,徐灿,徐江龙,田少辉,方川. 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[J].神经疾病与精神卫生,2024,(5).
DOI :10.3969/j. issn.1009-6574.2024.05.004.

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  • 在线发布日期: 2024-05-31