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免疫组织化学检测 YAP1 氨基端和羧基端可通过不同的染色模式突出显示胸腺瘤和高级别胸内上皮肿瘤的间变性。

Immunohistochemistry for YAP1 N-terminus and C-terminus highlights metaplastic thymoma and high-grade thymic epithelial tumors by different staining patterns.

机构信息

Department of Diagnostic Pathology, Kyoto University Hospital, 54 Shogoin Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.

Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

出版信息

Virchows Arch. 2024 Sep;485(3):461-469. doi: 10.1007/s00428-024-03888-4. Epub 2024 Aug 3.

Abstract

Metaplastic thymoma (MT), a rare subtype of thymic epithelial tumors (TETs), harbors YAP1::MAML2 fusions. Poroma, a skin tumor, also carries these fusions and exhibits a unique staining pattern for YAP1 immunohistochemistry (IHC), namely, a YAP1 N-terminus (YAP1[N])-positive but YAP1 C-terminus (YAP1[C])-negative pattern. In this context, MT was recently reported to lack YAP1(C) expression exclusively among TET subtypes. However, a lack of information about YAP1(N) expression in that study and another report that wild-type YAP1 expression was diminished in type B3 thymoma and thymic carcinoma warrants further studies for YAP1 expression in TETs. Thus, we immunohistochemically examined YAP1(N) and YAP1(C) staining patterns in our TET samples, including 14 cases of MT. In addition, 11 of the 14 MT cases were genetically analyzed with the formalin-fixed paraffin-embedded tissues if they harbored YAP1::MAML2 fusions. MT consistently exhibited YAP1(N)-positive and YAP(C)-negative staining, whereas type B3 thymoma and thymic carcinoma showed relatively heterogeneous staining patterns for YAP1(N) and YAP1(C) and were sometimes negative for both antibodies. Furthermore, a lower expression of YAP1 was found in type B3 compared to B2 thymomas. Among genetically analyzed 11 MT cases, 6 cases showed YAP1::MAML2 fusions, whereas the analysis failed in 5 very old cases due to poor RNA quality. These results indicate that IHC of both YAP1(N) and YAP1(C) is recommended to obtain staining patterns almost unique to MT. The biological significance of YAP1 in high-grade TETs warrants further investigation.

摘要

间变性胸腺瘤(MT)是胸腺瘤上皮肿瘤(TET)的一种罕见亚型,具有 YAP1::MAML2 融合。 汗孔瘤是一种皮肤肿瘤,也携带这些融合,并表现出 YAP1 免疫组化(IHC)的独特染色模式,即 YAP1[N] 阳性但 YAP1[C] 阴性。在这种情况下,最近有报道称 MT 是唯一缺乏 YAP1[C]表达的 TET 亚型。然而,该研究和另一项报道均缺乏关于 YAP1[N]表达的信息,且野生型 YAP1 表达在 B3 胸腺瘤和胸腺癌中减少,这使得需要进一步研究 TET 中的 YAP1 表达。因此,我们对包括 14 例 MT 在内的 TET 样本进行了 YAP1[N]和 YAP1[C]染色模式的免疫组化检查。此外,如果 14 例 MT 病例中的 11 例存在 YAP1::MAML2 融合,则对其进行了福尔马林固定石蜡包埋组织的基因分析。MT 始终表现出 YAP1[N]阳性和 YAP1[C]阴性染色,而 B3 胸腺瘤和胸腺癌的 YAP1[N]和 YAP1[C]染色模式相对异质,有时两者均为阴性。此外,B3 型与 B2 型胸腺瘤相比,YAP1 的表达水平较低。在经过基因分析的 11 例 MT 病例中,有 6 例显示 YAP1::MAML2 融合,而由于 RNA 质量差,5 例非常陈旧的病例分析失败。这些结果表明,建议对 YAP1[N]和 YAP1[C]进行免疫组化检查,以获得几乎仅见于 MT 的染色模式。YAP1 在高级 TET 中的生物学意义值得进一步研究。

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