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Extranodal NK/T-cell lymphoma (ENKTL), nasal type is an aggressive lymphoma characterized by rapid clinical progression, an unfavorable prognosis, and a short survival time. This study aimed to investigate the correlations of c-MYC protein expression, gene rearrangement, and gene copy number with the prognosis of ENKTL. Immunohistochemistry for CD20, CD3, CD56, TIA-1, Ki-67, and c-MYC were performed using tissue sections from 68 patients diagnosed with ENKTL. In situ hybridization was performed to detect Epstein-Barr virus (EBV)-encoded small RNA (EBER). c-MYC genetic alterations (located on chromosome 8q24) were detected using fluorescence in situ hybridization. Sixty patients with nasopharyngeal mucosa lymphadenosis were selected as a normal control group for the c-MYC gene and protein. Immunophenotypically, CD3 and TIA-1 were positive in all patients, CD56 was positive in 54 patients (79.4%), and CD20 was negative in all patients. A Ki-67 proliferation index of > 50% was observed in 94.1% of patients (64/68). In situ hybridization for EBER was positive in all patients. The c-MYC positive expression rate (> 40% of tumor cells with nuclear staining regarded as positive) in patients with ENKTL was 50% (34/68), which was significantly higher than that in patients with nasopharyngeal mucosa lymphadenosis (0%, 0/60; p < 0.05). Treatment efficacy was poor in patients with high c-MYC protein expression ( p < 0.05). Genetically, c-MYC rearrangements were not detected in any patients, but 26.5% (18/68) had increased c-MYC copy numbers. The gain of c-MYC copy numbers was positively correlated with c-MYC protein expression ( p < 0.05). Kaplan-Meier analysis illustrated that overall survival was significantly shorter in the c-MYC-positive group than in the c-MYC-negative group ( p < 0.05). Gain of c-MYC copy numbers was not associated with prognosis ( p > 0.05). Multivariate Cox regression analysis further confirmed that clinical stage and c-MYC positivity were independent prognostic factors in patients with ENKTL. The abnormal expression of c-MYC may play an important role in the development and progression of ENKTL and influence the prognosis of patients. [ABSTRACT FROM AUTHOR]