Heo Mi Hwa, Park Ha Young, Ko Young Hyeh, Kim Won Seog, Kim Seok Jin
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea.
J Cancer. 2017 Mar 29;8(6):1018-1024. doi: 10.7150/jca.17358. eCollection 2017.
Interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) is a member of the interferon regulatory factor family of transcriptional factors. Although IRF4/MUM1 expression is associated with aggressiveness of B-cell lymphoma and multiple myeloma, the prognostic value of IRF4/MUM1 expression in peripheral T-cell lymphoma (PTCL) is unclear. We analyzed a tissue array from 69 patients diagnosed with PTCL. The expression levels of IRF4/MUM1 and associated proteins such as MYC and Ikaros were analyzed by immunohistochemistry. Samples were classified by IRF4/MUM1 expression into a negative group (less than 5% of all tumor cells staining positive) or a positive group (≥ 5% of all tumor cells staining positive). IRF4/MUM1 expression was observed in 33% of all patients (23/69), most frequently in patients with anaplastic large cell lymphoma (ALCL, 78%, 7/9). Patients with PTCL, not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) showed expression rates of 33% (9/28) and 50% (4/8), respectively, whereas only 3 patients with extranodal NK/T-cell lymphoma (12%, 3/24) showed positive staining. The percentage of IRF4-positive tumor cells was significantly associated with the percentage of MYC-positive tumor cells (R: 0.410, P=0.013). Comparison of survival outcomes revealed that the IRF4/MUM1-positive group exhibited worse survival than the IRF4/MUM1-negative group; moreover, IRF4/MUM1-positive patients with a high level of MYC expression had the worst survival of all patients with nodal PTCL (PTCL-NOS, AITL, and ALCL; n=45) ( IRF4/MUM1 expression was associated with poor survival outcomes in PTCL, implying that this gene is a potential therapeutic target.
干扰素调节因子4（IRF4）/多发性骨髓瘤癌基因1（MUM1）是转录因子干扰素调节因子家族的成员。尽管IRF4/MUM1的表达与B细胞淋巴瘤和多发性骨髓瘤的侵袭性相关，但IRF4/MUM1表达在外周T细胞淋巴瘤（PTCL）中的预后价值尚不清楚。我们分析了69例诊断为PTCL患者的组织芯片。通过免疫组织化学分析IRF4/MUM1及相关蛋白如MYC和Ikaro的表达水平。样本根据IRF4/MUM1表达分为阴性组（所有肿瘤细胞染色阳性率低于5%）或阳性组（所有肿瘤细胞染色阳性率≥5%）。在所有患者的33%（23/69）中观察到IRF4/MUM1表达，最常见于间变性大细胞淋巴瘤（ALCL）患者（78%，7/9）。未另行分类的PTCL（PTCL-NOS）和血管免疫母细胞性T细胞淋巴瘤（AITL）患者的表达率分别为33%（9/28）和50%（4/8），而只有3例结外NK/T细胞淋巴瘤患者（12%，3/24）显示阳性染色。IRF4阳性肿瘤细胞的百分比与MYC阳性肿瘤细胞的百分比显著相关（R：0.410，P = 0.013）。生存结果比较显示，IRF4/MUM1阳性组的生存情况比IRF4/MUM1阴性组差；此外，MYC表达水平高的IRF4/MUM1阳性患者在所有结内PTCL患者（PTCL-NOS、AITL和ALCL；n = 45）中生存情况最差（IRF4/MUM1表达与PTCL患者的不良生存结果相关，这意味着该基因是一个潜在的治疗靶点。
