Usefulness of NF2 hemizygous loss detected by fluorescence in situ hybridization in diagnosing pleural mesothelioma in tissue and cytology material: A multi-institutional study
Usefulness of NF2 hemizygous loss detected by fluorescence in situ hybridization in diagnosing pleural mesothelioma in tissue and cytology material: A multi-institutional study
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DOI：
10.1016/j.lungcan.2022.11.013
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发表时间：
2022-11-25
期刊：
影响因子：
5.3
通讯作者：
Nabeshima，Kazuki
中科院分区：
文献类型：
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作者：
Sa-ngiamwibool，Prakasit;Hamasaki，Makoto;Nabeshima，Kazuki
目的BAP1、CDKN2A和NF2是胸膜间皮瘤中最常见的基因突变。区分PM和良性间皮细胞增殖(BMP)有时是具有挑战性的；众所周知，通过免疫组织化学(IHC)确定的BAP1丢失和通过荧光原位杂交(FISH)确定的CDKN2杂合性缺失(HD)是有用的。然而，关于NF2FISH在PM中的诊断作用的数据是有限的。材料和方法收集多机构PM病例，包括106例手术标本和107例细胞块标本，37例良性间皮细胞增殖(BMP)组织和31例反应性间皮细胞(RMC)病例，用免疫组织化学方法分析BAP1的NF2改变和CDKN2A和NF2的FISH。CDKN2AHD和BAP1缺失率分别为75.5%/65.4%和63.6%/60%。BMP或RMC未显示BAP1丢失、CDKN2AHD或NF2HL。联合应用BAP1缺失、CDKN2AHD和NF2HL可提高诊断PM和BMP的敏感性，其敏感性分别为98.1%TC/94.4%CBC。BAP1缺失、CDKN2AHD或NF2HL在上皮样PM中分别为69%、70%和58%，而在肉瘤样PM中分别为9%、91%和27%。组织类型、组织学分级和CDKN2A缺失状态在总存活率方面有显著差异，而BAP1缺失和NF2HL则无显著差异。结论NF2HL在PM的TC和CBC中均可通过FISH检测到，尤其是当BAP1缺失和CDKN2AHD联合检测时，NF2HL是一种有效的鉴别PM和BMP的方法。
ObjectivesBAP1,CDKN2A, andNF2are the most frequently altered genes in pleural mesotheliomas (PM). Discriminating PM from benign mesothelial proliferation (BMP) is sometimes challenging; it is well established that BAP1 loss, determined by immunohistochemistry (IHC), andCDKN2Ahomozygous deletion (HD), determined by fluorescence in situ hybridization (FISH), are useful. However, data regarding the diagnostic utility ofNF2FISH in PM is limited. Thus, we performed a multi-institutional study examining the utility ofNF2alterations determined by FISH for diagnosing PM in combination with BAP1 loss andCDKN2AHD.Materials and methodsMulti-institutional PM cases, including 106 surgical and 107 cell block samples as well as 37 tissue cases of benign mesothelial proliferation (BMP) and 31 cell block cases with reactive mesothelial cells (RMC), were collected and analyzed using IHC for BAP1 and FISH forCDKN2AandNF2.ResultsIn PM,NF2FISH revealed hemizygous loss (HL) in 54.7% of tissue cases (TC) and 49.5% of cell block cases (CBC), with about 90% of HL being monosomy.CDKN2AHD or BAP1 loss were detected in 75.5%/65.4% TC or 63.6%/60% CBC, respectively. BMP or RMC showed no BAP1 loss,CDKN2AHD, orNF2HL. For discriminating PM from BMP, a combination of BAP1 loss,CDKN2AHD, andNF2HL yielded enhanced sensitivity of 98.1% TC/94.4% CBC. BAP1 loss,CDKN2AHD, orNF2HL were observed in 69%, 70%, or 58% of epithelioid PM, but in 9%, 91%, or 27% of sarcomatoid PM, respectively. Histotype, histological gradings, andCDKN2Adeletion status showed significant differences in overall survival, while BAP1 loss andNF2HL did not.ConclusionNF2HL, consisting predominantly of monosomy, can be detected by FISH in both TC and CBC of PM, and is effective for distinguishing PM from BMP, especially when combined with BAP1 loss andCDKN2AHD.