J Cancer 2017; 8(6):1018-1024. doi:10.7150/jca.17358
IRF4/MUM1 expression is associated with poor survival outcomes in patients with peripheral T-cell lymphoma
1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;
2. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
3. Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea.
Heo MH, Park HY, Ko YH, Kim WS, Kim SJ. IRF4/MUM1 expression is associated with poor survival outcomes in patients with peripheral T-cell lymphoma. J Cancer 2017; 8(6):1018-1024. doi:10.7150/jca.17358. Available from http://www.jcancer.org/v08p1018.htm
Background: 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.
Methods: 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).
Results: 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) (P < 0.05).
Conclusions: IRF4/MUM1 expression was associated with poor survival outcomes in PTCL, implying that this gene is a potential therapeutic target.
Keywords: IRF4, MUM1, PTCL