Departments of Histopathology and Internal Medicine.
Post Graduate Institute of Medical Education & Research (PGIMER), Sector-12, Chandigarh, India.
Appl Immunohistochem Mol Morphol. 2021 Oct 1;29(9):648-656. doi: 10.1097/PAI.0000000000000936.
The anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a clinically distinct but heterogeneous entity and lacks the specific immunophenotypic or genetic features compared with the ALK-positive ALCL. Recent molecular studies have provided genetic landscapes of ALK-negative ALCL that have prognostic significance. In this study, we subtyped ALK-negative ALCL based on DUSP22 rearrangements and TP63 expression and also looked for mutations in JAK-STAT pathway. The subtyping of the ALK-negative ALCL in relation to DUSP22 rearrangement and TP63 expression was done using fluorescence in situ hybridization and immunohistochemistry, respectively. The hotspot JAK-STAT mutations were analyzed using Sanger sequencing and amplification refractory mutation system polymerase chain reaction (PCR) and Signal transducer and activator of transcription 3 (STAT3) expression by immunohistochemistry. Forty-eight cases of ALCL were included with median age of 30 years and sex ratio of 1.8:1. The p63 expression was detected in 26.7% of ALK-negative ALCL cases. DUSP22 rearrangement was noted in 12.5% cases of p63-negative ALK-negative ALCLs. DUSP22 rearranged cases had better overall survival in contrast to p63 expressing and triple negative ALCLs. Triple negative ALCLs showed inferior overall survival rate. STAT3 expression was evident in 61.1% and 60% of ALK-positive and ALK-negative ALCLs, respectively. None of the cases subjected to Sanger sequencing as well as amplification refractory mutation system PCR for hotspot mutation analysis of JAK1 (exon 24) and STAT3 (exon 21) revealed any mutation. ALK-negative ALCL is a genetically heterogeneous disease with widely disparate clinical outcomes. Subtyping of ALK-negative ALCL based on DUSP22 rearrangement and p63 expression provides prognostic information.
间变性大细胞淋巴瘤（ALCL）是一种临床特征明显但具有异质性的实体瘤，与间变性大细胞淋巴瘤（ALK 阳性）相比，缺乏特定的免疫表型或遗传特征。最近的分子研究为具有预后意义的 ALK 阴性 ALCL 提供了遗传图谱。在这项研究中，我们根据 DUSP22 重排和 TP63 表达对 ALK 阴性 ALCL 进行了亚型分类，并寻找 JAK-STAT 通路中的突变。ALK 阴性 ALCL 的亚型分类分别使用荧光原位杂交和免疫组化检测 DUSP22 重排和 TP63 表达。使用 Sanger 测序和扩增受阻突变系统聚合酶链反应（PCR）分析热点 JAK-STAT 突变，使用免疫组化分析信号转导和转录激活因子 3（STAT3）表达。纳入 48 例 ALCL 患者，中位年龄为 30 岁，男女比例为 1.8:1。26.7%的 ALK 阴性 ALCL 病例检测到 p63 表达。p63 阴性 ALK 阴性 ALCL 中有 12.5%的病例存在 DUSP22 重排。与 p63 表达和三阴性 ALCL 相比，DUSP22 重排的病例具有更好的总生存率。三阴性 ALCL 的总生存率较差。ALK 阳性和 ALK 阴性 ALCL 的 STAT3 表达率分别为 61.1%和 60%。对 JAK1（外显子 24）和 STAT3（外显子 21）热点突变分析进行 Sanger 测序和扩增受阻突变系统 PCR 的病例均未发现任何突变。ALK 阴性 ALCL 是一种遗传异质性疾病，具有广泛不同的临床结局。基于 DUSP22 重排和 p63 表达对 ALK 阴性 ALCL 进行亚型分类可提供预后信息。
