目标:BAP1、CDKN2A、和NF2是胸膜间皮瘤(PM)中最常见的基因。将PM与良性间皮增殖(BMP)区分开来有时是具有挑战性的;众所周知,BAP1丢失,通过免疫组织化学(IHC)确定,和CDKN2A纯合缺失(HD),通过荧光原位杂交(FISH)确定,是有用的。然而,有关NF2FISH在PM中的诊断效用的数据有限。因此,我们进行了一项多机构研究,检查了FISH确定的NF2改变在联合BAP1丢失和CDKN2AHD诊断PM中的效用.
方法:多机构PM案例,包括106例手术和107例细胞块样本,以及37例良性间皮增生(BMP)组织和31例反应性间皮细胞(RMC)细胞块病例,收集并使用IHC分析BAP1和FISH分析CDKN2A和NF2。
结果:在下午,NF2FISH在54.7%的组织病例(TC)和49.5%的细胞阻滞病例(CBC)中显示出半合子丢失(HL),其中约90%的HL是一元性的。在75.5%/65.4%TC或63.6%/60%CBC中检测到CDKN2AHD或BAP1丢失,分别。BMP或RMC显示无BAP1损失,CDKN2AHD,或NF2HL。为了区分PM和BMP,BAP1损失的组合,CDKN2AHD,NF2HL的敏感性增强为98.1%TC/94.4%CBC。BAP1损失,CDKN2AHD,或NF2HL在69%中观察到,70%,或58%的上皮样PM,但在9%中,91%,或27%的肉瘤样PM,分别。组织型,组织学分级,和CDKN2A缺失状态显示出总生存率的显着差异,而BAP1丢失和NF2HL没有。
结论:NF2HL,主要由一元性组成,可以通过FISH在PM的TC和CBC中检测到,并有效区分PM和BMP,特别是与BAP1丢失和CDKN2AHD结合时。
BAP1,
CDKN2A, and NF2 are 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), and CDKN2A homozygous deletion (HD), determined by fluorescence in situ hybridization (FISH), are useful. However, data regarding the diagnostic utility of NF2 FISH in PM is limited. Thus, we performed a multi-institutional
study examining the utility of NF2 alterations determined by FISH for diagnosing PM in combination with BAP1 loss and
CDKN2A HD.
Multi-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 for CDKN2A and NF2.
In PM, NF2 FISH 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.
CDKN2A HD or BAP1 loss were detected in 75.5%/65.4% TC or 63.6%/60% CBC, respectively. BMP or RMC showed no BAP1 loss,
CDKN2A HD, or NF2 HL. For discriminating PM from BMP, a combination of BAP1 loss, CDKN2A HD, and NF2 HL yielded enhanced sensitivity of 98.1% TC/94.4% CBC. BAP1 loss, CDKN2A HD, or NF2 HL were observed in 69%, 70%, or 58% of epithelioid PM, but in 9%, 91%, or 27% of sarcomatoid PM, respectively. Histotype, histological gradings, and CDKN2A deletion status showed significant differences in overall survival, while BAP1 loss and NF2 HL did not.
NF2 HL, 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 and CDKN2A HD.