Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Cancer Sci. 2019 Aug;110(8):2600-2606. doi: 10.1111/cas.14109. Epub 2019 Jul 11.
The t(11;14)/CCND1-IGH, t(4;14)/NSD2(MMSET)-IGH, and t(14;16)/IGH-MAF gene 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 detecting CCND1, NSD2, and MAF gene 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, and MAF gene rearrangements were estimated accurately by IHC, suggesting that conventional FISH assays can be replaced by IHC.
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-MAF 基因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) 更加经济高效，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，我们使用 FFPE 标本进行组织 FISH 和 IHC 检测，并研究了 IHC 作为检测 CCND1、NSD2 和 MAF 基因重排的工具的有用性。在组织 FISH 和 IHC 分析中，CD138 信号用于识别浆细胞。使用队列 1（n=70），我们首先进行了组织 FISH，然后进行了 IHC，并确定了 IHC 的截断值。在该队列中，3 种分子的敏感性和特异性分别≥.90 和≥.96。在队列 2 中，我们使用基因状态未知的 MM 病例（n=120）进行 IHC，并使用队列 1 确定的截断值来估计基因状态。随后的 FISH 分析表明，3 种分子的敏感性和特异性分别≥.92 和≥.98。IHC 准确估计了 CCND1、NSD2 和 MAF 基因重排，表明可以用 IHC 替代传统的 FISH 检测。
