4级IDH突变型星形细胞瘤的分子病理学及组织病理学特征分析
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北京市神经外科研究所科研培育基金(2022 改革与发展项目 - 所自然 -1)


Genetic alterations and histopathological features of IDH-mutant astrocytoma grade 4
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    摘要:

    目的 探讨 4 级异柠檬酸脱氢酶(IDH)突变型星形细胞瘤的分子病理学及组织病理学特 征。方法 选取 2021 年 7 月至 2022 年 7 月于首都医科大学附属北京天坛医院神经外科接受手术治疗, 术后病理学整合诊断为 4 级 IDH 突变型星形细胞瘤的 73 例患者为研究对象,分析患者的流行病学及肿 瘤的组织病理学特点。采用二代测序的方法检测肿瘤分子病理学特征;采用免疫组织化学染色检测肿 瘤细胞特征性的蛋白表达。结果 73 例 4 级 IDH 突变型星形细胞肿瘤患者的中位发病年龄为 38 岁;男 性占 56.2%(41/73);75.3%(55/73)肿瘤位于额叶。形态学结果显示,13.7%(10/73)的肿瘤在镜下未见微 血管增生和坏死,表现为 2 级或 3 级星形细胞瘤的形态,其他 86.3%(63/73)的肿瘤可见微血管增生和坏 死,符合 4 级星形细胞瘤的特点。免疫组化染色结果显示,73 例肿瘤 IDH1 R132H 染色均为弥漫阳性, P53 蛋白表达阳性率为 88.1%(59/67),α- 地中海贫血 / 精神发育迟滞综合征 X 染色体相关基因(ATRX) 表达缺失率为 83.6%(56/67)。分子病理学检测结果显示,所有患者均为 IDH1 R132H 突变,76.7%(56/73) 的患者 O-6- 甲基鸟嘌呤 -DNA 甲基转移酶启动子区发生甲基化,TP53 和 ATRX 基因的突变率分别为 96.6%(57/59)和 64.3%(36/56),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 46.6%(34/73)。结论 4 级 IDH 突变型星形细胞瘤在组织病理学方面大部分有坏死和血管增生等 高级别肿瘤的特点,少数病例有较低级别星形细胞瘤形态伴分子病理学 CDKN2A/B 纯合性缺失的特点。 对于 IDH 突变型的星形细胞瘤,进行包括 CDKN2A/B 拷贝数在内的分子病理检测是有必要的。

    Abstract:

    Objective To investigate the genetic alterations and histopathological features of IDHmutant astrocytoma grade 4. Methods From July 2021 to July 2022, in the Department of Neurosurgery of Beijing Tiantan Hospital affiliated to Capital Medical University, a total of 73 patients were recruited, who undertook surgery treatment and diagnosed as IDH-mutant astrocytoma grade 4 by postoperative histopathology. These cases' epidemiological and morphological characteristics were gathered and studied. The second generation sequencing method was used to detect the molecular pathology characteristics of tumors; Immunohistochemical staining was used to detect the characteristic protein expression in tumor cells. Results The median age of the IDH-mutant astrocytoma grade 4 patients (n=73) was 38 years old, male accounting for 56.2% (41/73). 75.3% (55/73) of the tumors were in the frontal lobes. Necrosis and/or microvascular proliferation were absent in 13.7% of the tumors, which histopathological grade conforms to grade 2/3 astrocytoma. Other 86.3% (63/73) of tumors showed microvascular proliferation and necrosis, consistent with the characteristics of grade 4 astrocytoma. Immunohistochemistrical examination revealed significant IDH R132H positivity in the 73 tumors. The positive rate of P53 was 88.1% (59/67). The loss of ATRX (α-thalassemia/mental retardation, X-linked) expression is 83.6% (56/67). Molecular pathology test results showed that all patients had IDH1 R132H mutation. The promoter region of O-6-methylguanine DNA methyltransferase was methylated in 76.7% (56/73) of patients, and the mutation rate of TP53 and ATRX was 96.6% (57/59) and 64.3% (36/56) respectively. The proportion of homozygous deletion of cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) was 46.6% (34/73). Conclusions Necrosis and/or microvascular proliferation can be seen in the majority of grade 4 IDHmutant astrocytomas. However, some cases with homozygous CDKN2A/2B deletion displayed morphological characteristics aligned to lower-grade astrocytomas. For IDH mutant astrocytomas, molecular pathological testing including CDKN2A/B copy number is necessary.

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陈慧媛,刘幸,崔云,李桂林.4级IDH突变型星形细胞瘤的分子病理学及组织病理学特征分析[J].神经疾病与精神卫生,2023,23(5):
DOI :10.3969/j. issn.1009-6574.2023.05.006.

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  • 在线发布日期: 2023-06-19