Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma
Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma
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DOI：
10.1002/cncy.22409
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发表时间：
2021-01-25
影响因子：
3.4
通讯作者：
Nabeshima, Kazuki
中科院分区：
文献类型：
--
作者：
Kinoshita, Yoshiaki;Hamasaki, Makoto;Nabeshima, Kazuki
背景恶性胸膜间皮瘤(MPM)以多个基因突变为特征，包括位于9p21位点的细胞周期蛋白依赖的激酶抑制因子2A/p16、位于22q12位点的BRCA1相关蛋白1(BAP1)和神经纤维瘤病2型(NF2)。最近的研究表明，荧光原位杂交(FISH)检测MPM组织标本中NF2的半合子缺失。作者研究了NF2 FISH单独或与其他诊断方法(9p21 FISH、甲硫腺苷磷酸酶[MTAP]免疫组织化学[IHC]和BAP1 IHC)联合使用是否能有效区分胸腔积液细胞块中的MPM细胞和反应性间皮细胞(RMC)。结果NF2半合子缺失(22号染色体单体或缺失)鉴别MPM和RMC的敏感性为51.9%(22号染色体单体48.1%，缺失3.7%)，特异性100%。NF2 FISH、9p21 FISH和BAP1 IHC联合检测的敏感性(98.1%)高于任何一种检测方法(9p21 FISH，61.1%；MTAP IHC，52.8%；或BAP1 IHC，60.4%)。细胞块中半合子NF2丢失水平与相应组织中NF2丢失水平呈正相关。此外，为了克服细胞学标本的特异性挑战，25.9%的MPM病例需要FISH和细胞角蛋白AE1/AE3免疫荧光来进行FISH检测主要分散的MPM细胞。结论NF2 FISH或联合其他诊断方法可以有效区分胸腔积液细胞块中的MPM细胞和RMC。
Background Malignant pleural mesothelioma (MPM) is characterized by mutations in several genes, including cyclin-dependent kinase-inhibitor 2A/p16 in the 9p21 locus, BRCA1-associated protein 1 (BAP1), and neurofibromatosis type 2 (NF2) in the 22q12 locus. Recent studies indicate that fluorescence in situ hybridization (FISH) detects hemizygous loss of NF2 in tissue specimens of MPM. The authors investigated whether NF2 FISH, either alone or in combination with other diagnostic assays (9p21 FISH, methylthioadenosine phosphorylase [MTAP] immunohistochemistry [IHC], and BAP1 IHC), effectively distinguishes MPM cells from reactive mesothelial cells (RMCs) in cell blocks prepared from pleural effusions.Methods FISH assays were used to examine the deletion status of NF2 and 9p21, and IHC was used to determine the expression of MTAP and BAP1 in cell blocks from 54 cases with MPM and 18 cases with RMCs.Results Hemizygous NF2 loss (chromosome 22 monosomy or hemizygous deletion) showed 51.9% sensitivity (48.1% for chromosome 22 monosomy and 3.7% for hemizygous deletion) and 100% specificity in differentiating MPM cells from RMCs. Combinations of NF2 FISH, 9p21 FISH, and BAP1 IHC assays yielded greater sensitivity (98.1%) than any assay alone (9p21 FISH, 61.1%; MTAP IHC, 52.8%; or BAP1 IHC, 60.4%). The level of hemizygous NF2 loss in cell blocks positively correlated with that in corresponding tissues. Furthermore, to overcome cytologic specimen-specific challenges, FISH combined with cytokeratin AE1/AE3 immunofluorescence was necessary in 25.9% of MPM cases for FISH assessment of predominantly scattered MPM cells.Conclusions NF2 FISH alone or in combination with other diagnostic assays effectively differentiates MPM cells from RMCs in cell blocks prepared from pleural effusions.