临床与病理杂志2024，Vol.44Issue(10)：1359-1367,9.DOI:10.11817/j.issn.2095-6959.2024.240802
12例幕上室管膜瘤患者临床病理特征及分子遗传学改变
Clinicopathological characteristics and molecular genetic alterations in 12 patients with supratentorial ependymoma
摘要
Abstract
Objective:Supratentorial ependymoma is currently classified into zinc finger translocation-associated(ZFTA)fusion-positive and Yes-associated protein 1(YAP1)fusion-positive subtypes.Molecular subtyping provides a more accurate prognostic prediction than histological subtyping.This study aims to explore the clinicopathological features and molecular genetic alterations in patients with supratentorial ependymoma. Methods:A retrospective analysis was performed on 12 patients with a confirmed diagnosis of supratentorial ependymoma at the First Affiliated Hospital of Xinjiang Medical University from January 2022 to December 2023. Results:Among the 12 patients,5 were male and 7 were female;the age at onset ranged from 4 to 58 years,with an average of 29 years and a median of 30 years;tumor diameters ranged from 1.10 to 9.60 cm,with an average diameter of 4.57 cm.According to the World Health Organization(WHO)histopathological grading for central nervous system ependymoma,10 patients were grade Ⅲ and 2 patients were grade Ⅱ.Eleven patients underwent total tumor resection,and 1 patient underwent subtotal resection.Postoperatively,4 patients received both radiotherapy and chemotherapy,3 received radiotherapy alone,and 5 received neither radiotherapy nor chemotherapy.Follow-up data were available for all 12 patients,with follow-up durations ranging from 3 to 25 months(average 10.5 months,median 9 months);at the end of follow-up,2 patients had died while 10 remained progression-free.Immunohistochemical analysis showed variable positive expression of glial fibrillary acidic protein(GFAP)in the cytoplasm and membrane of tumor cells;6 patients showed variable positive expression of oligodendrocyte transcription factor 2(Olig2)and 6 patients showed perinuclear punctate positive expression of epithelial membrane antigen(EMA).In 2 patients,L1 cell adhesion molecule(L1CAM)was variably positive in the cytoplasm and membrane,and in 4 patients,nuclear expression of nuclear κ-light chain enhancer of activated B cells P65(NF-κB P65,also known as RELA)was observed;no loss of alpha thalassemia/mental retardation syndrome X-linked(ATRX)expression was noted;isocitrate dehydrogenase 1(IDH1)was not expressed in tumor cells,and the Ki-67 proliferation index ranged from 3％to 60％.Next-generation sequencing(NGS)results showed that 7 patients harbored a C11orf95(ZFTA)-RELA fusion,of which 3 patients were accompanied by a homozygous deletion of cyclin-dependent kinase inhibitor 2A/B(CDKN2A/B),and 2 patients had a fusion between fibroblast growth factor receptor 1 and transforming acidic coiled-coil containing protein 1(FGFR1-TACC1);3 patients exhibited an FGFR1-TACC1 fusion,with 1 patient further harboring a fusion between quaking homolog,KH domain RNA binding protein and Raf-1 proto-oncogene,serine/threonine kinase(QKI-RAF1).Molecular diagnostic results classified 7 patients as supratentorial ependymomas,ZFTA fusion-positive;4 patients as ependymomas,NEC(not classifiable as either ZFTA or YAP1 subtype);and 1 patient was re-diagnosed as pediatric diffuse low-grade glioma. Conclusion:In supratentorial ependymoma,ZFTA frequently fuses with RELA and may be accompanied by multiple gene alterations;the presence of a homozygous deletion of CDKN2A/B suggests a potentially poorer prognosis.关键词
幕上室管膜瘤/分子遗传学/临床病理特征/基因融合/中枢神经系统肿瘤Key words
supratentorial ependymoma/molecular genetics/clinical pathological features/gene fusion/central nervous system tumors引用本文复制引用
黄钰,张巍,薛晶,苏丽萍..12例幕上室管膜瘤患者临床病理特征及分子遗传学改变[J].临床与病理杂志,2024,44(10):1359-1367,9.基金项目
新疆维吾尔自治区自然科学基金(2022D01D072) （2022D01D072）
省部共建中亚高发病成因与防治国家重点实验室开放课题——精准医学项目(SKL-2022-JZ7).This work was supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01D072)and State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(SKL-2022-JZ7),China. （SKL-2022-JZ7）
