荧光原位杂交检测骨与软组织肿瘤EWSR1基因重排的临床应用价值及不典型信号分析  

Detection of EWSR1 gene rearrangement by fluorescence in situ hybridization in bone and soft tissue tumors:clinical application evaluation and atypical signal analysis

作　　者：李兰 张铭 张婷婷 丁宜 Li Lan;Zhang Ming;Zhang Tingting;Ding Yi(Department of Pathology,Beijing Jishuitan Hospital,Capital Medical University,Beijing 100035,China)

机构地区：[1]首都医科大学附属北京积水潭医院病理科,北京100035

出　　处：《中华病理学杂志》2024年第5期458-463,共6页Chinese Journal of Pathology

基　　金：北京市属医院科研培育计划项目(PX2023014);首都医科大学附属北京积水潭医院“学科骨干”计划专项经费资助(XKGG202205)。

摘　　要：目的探讨应用荧光原位杂交(FISH)检测骨与软组织肿瘤EWSR1基因重排的临床应用价值并对出现不典型信号的病例进行分析。方法收集首都医科大学附属北京积水潭医院2014—2021年应用FISH检测EWSR1基因重排的病例,分析其用于诊断相关骨与软组织肿瘤的临床应用价值并对FISH检测结果呈不典型信号的病例进行二代测序以进一步分析。结果应用FISH检测EWSR1基因重排病例211例,检测成功205例(205/211,97%),失败6例(6/211,3%)。6例检测失败病例中,4例因骨组织脱钙不当未检测到荧光信号,1例因切片太厚信号重叠无法判读,1例因信号扩增且杂乱无法判读。205例检测成功病例中,阳性122例(122/205,59%),不典型阳性8例(8/205,4%),阴性75例(75/205,37%)。阳性者其阳性细胞百分数为34%~98%,其中120例(120/122,98%)阳性细胞百分数>50%。205例检测成功病例中,156例组织学诊断为尤因肉瘤,其中阳性110例(110/156,71%),不典型阳性7例(7/156,4%),阴性39例(39/156,25%)。9例组织学诊断为软组织透明细胞肉瘤,其中阳性6例(6/9),不典型阳性1例(1/9),阴性2例(2/9)。5例组织学诊断为骨外黏液样软骨肉瘤,其中阳性2例(2/5),阴性3例(3/5)。3例组织学诊断为血管瘤样纤维组织细胞瘤,其中阳性2例(2/3),阴性1例(1/3)。2例组织学诊断为软组织肌上皮瘤,其中阳性1例(1/2),阴性1例(1/2)。1例组织学诊断为嗅神经母细胞瘤,结果为阳性。检测其他肿瘤29例,包括骨肉瘤、滑膜肉瘤、恶性黑色素瘤等,均为阴性。以组织学为金标准,将不典型阳性按阴性考虑,以29例其他肿瘤为对照组病例,检测EWSR1基因重排诊断尤因肉瘤的灵敏度为71%,特异度为100%;诊断软组织透明细胞肉瘤的灵敏度为67%,特异度为100%;诊断骨外黏液样软骨肉瘤的灵敏度为40%,特异度为100%;诊断血管瘤样纤维组织细胞瘤的灵敏度为67%,特异度为100%;诊断软组织肌上皮瘤的灵敏度为50%,特异度�Objective To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization(FISH)in bone and soft tissue tumors and to analyze the cases with atypical signal pattern.Methods The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital,Capital Medical University from 2014 to 2021 were collected,and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed.The cases with atypical positive signals were further analyzed by next generation sequencing(NGS).Results FISH using EWSR1 break-apart probe kit was successfully performed in 97%(205/211)of cases,6 cases failed.Four of the 6 failures were due to improper decalcification,1 case due to signal overlap caused by thick slices,and 1 case due to signal amplification and disorder.EWSR1 gene rearrangements were positive in 122 cases(122/205,59%),atypical positive signal in 8 cases(8/205,4%),and negative in 75 cases(75/205,37%).In cases testing positive,the percentage of positive cells ranged from 34%to 98%,with 120 cases(120/122,98%)showing a positive cell percentage greater than 50%.Among the 205 successfully tested cases,156 cases were histologically diagnosed as Ewing′s sarcoma,of which 110 were positive(110/156,71%),7 were atypical positive(7/156,4%),and 39 were negative(39/156,25%).Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue,of which 6 were positive(6/9),1 was atypical positive(1/9),and 2 were negative(2/9).Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma,of which 2 were positive(2/5)and 3 were negative(3/5).Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma,of which 2 were positive(2/3)and 1 was negative(1/3).Two cases were histologically diagnosed as myoepithelioma of soft tissue,of which 1 was positive(1/2)and 1 was negative(1/2).One case was histologically diagnosed as olfactory neuroblastoma with a positive result.The 29 other tumor cases including osteosarcoma

关 键 词：骨肿瘤 软组织肿瘤 原位杂交 荧光 基因重排 

分 类 号：R738.6[医药卫生—肿瘤]