荧光原位杂交检测COL1A1-PDGFB隐匿性融合的隆突性皮肤纤维肉瘤临床病理及遗传学分析  

Cryptic COL1A1-PDGFB fusion in dermatofibrosarcoma protuberans:a clinicopathological and genetic analysis

作　　者：陈敏[1] 陈玉梅 陆杨[1] 何鑫[1] 彭恒 张红英[1] Chen Min;Chen Yumei;Lu Yang;He Xin;Peng Heng;Zhang Hongying(Department of Pathology,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院病理科,成都610041

出　　处：《中华病理学杂志》2023年第1期13-18,共6页Chinese Journal of Pathology

基　　金：国家自然科学基金面上项目(81972520);四川大学华西医院学科卓越发展1·3·5工程临床研究孵化项目(2018HXFH011)。

摘　　要：目的探讨荧光原位杂交(FISH)检测COL1A1-PDGFB隐匿性融合的隆突性皮肤纤维肉瘤(cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans, CC-DFSP)的临床病理及分子遗传学特征。方法收集四川大学华西医院2021年1至9月诊断的3例CC-DFSP, 总结其临床病理特征, 行二代测序、逆转录-聚合酶链反应(RT-PCR)及Sanger测序进一步验证, 并复习相关文献。结果 3例患者2例女性、1例男性, 年龄分别为29、44和32岁, 发病部位分别为腹壁、阴阜和肩胛。3例CC-DFSP具典型隆突性皮肤纤维肉瘤(dermatofibrosarcoma protuberans, DFSP)形态, 肿瘤边界不清, 浸润真皮或皮下脂肪组织, 肿瘤细胞呈梭形、短梭形, 并排列呈席纹状结构。3例肿瘤细胞CD34弥漫阳性, S-100蛋白、平滑肌肌动蛋白、Myogenin阴性, H3K27me3无缺失, Ki-67阳性指数10%~15%。FISH均未检出PDGFB重排及COL1A1-PDGFB融合, 但检出COL1A1重排。例1经二代测序、RT-PCR及Sanger测序显示COL1A1第31号外显子-PDGFB第2号外显子融合及COL1A1扩增。3例患者均行扩大手术切除, 例3手术切除后2年复发, 余无复发及转移。结论 FISH检测PDGFB重排及COL1A1-PDGFB融合已广泛应用于临床病理工作中。若遇到病理形态高度怀疑为DFSP而常规FISH检测阴性的病例时, 建议加做其他分子检测如二代测序或至少行FISH检测COL1A1基因重排进一步分析, 有助于发现隐匿性COL1A1-PDGFB融合甚至其他罕见融合。Objective To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans(CC-DFSP).Methods Three cases of CC-DFSP diagnosed in West China Hospital,Sichuan University,Chengdu,China from January 2021 to September 2021 were studied.Immunohistochemistry for CD34 and other markers,fluorescence in situ hybridization(FISH)for PDGFB,COL1A1-PDGFB and COL1A1,next-generation sequencing(NGS),reverse-transcriptase polymerase chain reaction(RT-PCR)and Sanger sequencing were performed.Results There were three cases of CC-DFSP,including two females and one male.The patients were 29,44 and 32 years old,respectively.The sites were abdominal wall,caruncle and scapula.Microscopically,they were poorly circumscribed.The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues,typically arranging in a storiform pattern.Immunohistochemically,the neoplastic cells exhibited diffuse CD34 expression,but were negative for S-100,SMA,and Myogenin.Loss of H3K27me3 was not observed in the tumor cells.The Ki-67 index was 10%-15%.The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion,whereas showing unbalanced rearrangement for COL1A1.Case 1 showed a COL1A1(exon 31)-PDGFB(exon 2)fusion using NGS,which was further validated through RT-PCR and Sanger sequencing.All patients underwent extended surgical resection.Except for case 3 with recurrence 2 years after surgical resection,the other 2 cases showed no recurrence or metastasis during the follow-up.Conclusions FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection.However,for cases with negative routine FISH screening that were highly suspicious for DFSPs,supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.

关 键 词：软组织肿瘤 基因融合 原位杂交 荧光 隆突性皮肤纤维肉瘤 

分 类 号：R739.5[医药卫生—肿瘤]