Immunohistochemistry for identification ofCCND1,NSD2, andMAFgene rearrangements in plasma cell myeloma
Immunohistochemistry for identification ofCCND1,NSD2, andMAFgene rearrangements in plasma cell myeloma
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免疫组织化学鉴定浆细胞骨髓瘤中 CCND1、NSD2 和 MAF 基因重排
DOI：
10.1111/cas.14109
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发表时间：
2019
期刊：
影响因子：
5.7
通讯作者：
Inagaki Hiroshi
中科院分区：
文献类型：
--
作者：
Murase Takayuki;Ri Masaki;Narita Tomoko;Fujii Keiichiro;Masaki Ayako;Iida Shinsuke;Inagaki Hiroshi
荧光原位杂交（FISH）检测到的t(11;14)/CCND1‐IGH、t(4;14)/NSD2（MMSET）‐IGH和t(14;16)/IGH‐MAFgene重排用于多发性骨髓瘤（MM）患者的风险分层。与使用新鲜细胞的传统FISH技术相比，免疫组织化学（IHC）具有更高的成本和时间效率，并且可以很容易地应用于常规制备的福尔马林固定石蜡包埋（FFPE）材料。在这项研究中，我们利用FFPE标本进行了组织FISH和免疫组化，并检验了免疫组化作为检测ccnd1、NSD2和mafgene重排工具的有效性。CD138信号在组织FISH和IHC分析中用于鉴定浆细胞。在队列1 （n = 70）中，我们进行了组织FISH和随后的免疫组化，并确定了免疫组化的截断点。在本队列中，这3种分子的敏感性和特异性分别为≥0.90和≥0.96。在队列2中，使用未知基因状态的MM病例（n = 120）进行免疫组化，并使用队列1确定的截断点估计基因状态。随后的FISH分析显示，这3个分子的敏感性和特异性分别为≥0.92和≥0.98。通过免疫组化可以准确估计CCND1、NSD2和mafgene重排，这表明免疫组化可以取代传统的FISH检测。
The t(11;14)/CCND1‐IGH, t(4;14)/NSD2(MMSET)‐IGH, and t(14;16)/IGH‐MAFgene rearrangements detected by fluorescence in situ hybridization (FISH) are used for risk stratification in patients with multiple myeloma (MM). Compared with conventional FISH techniques using fresh cells, immunohistochemistry (IHC) is much more cost‐ and time‐efficient, and can be readily applied to routinely prepared formalin‐fixed, paraffin‐embedded (FFPE) materials. In this study, we performed tissue FISH and IHC employing FFPE specimens, and examined the usefulness of IHC as a tool for detectingCCND1,NSD2, andMAFgene rearrangements. CD138 signals were used to identify plasma cells in tissue FISH and IHC analyses. With cohort 1 (n = 70), we performed tissue FISH and subsequently IHC, and determined IHC cut‐off points. In this cohort, the sensitivity and specificity for the 3 molecules were ≥.90 and ≥.96, respectively. With cohort 2, using MM cases with an unknown gene status (n = 120), we performed IHC, and the gene status was estimated using the cut‐off points determined with cohort 1. The subsequent FISH analysis showed that the sensitivity and specificity for the 3 molecules were ≥.92 and ≥.98, respectively.CCND1, NSD2, andMAFgene rearrangements were estimated accurately by IHC, suggesting that conventional FISH assays can be replaced by IHC.