Abstract
Purpose
c-MYC plays an important role in regulating cellular growth and apoptosis, and it is aberrantly expressed in many human malignancies. Although c-MYC has been extensively investigated in Burkitt lymphoma and diffuse large B cell lymphoma, little has been reported in anaplastic large cell lymphoma (ALCL). The aim of this study was to investigate the expression and genetic alterations of c-MYC in primary systemic ALCL, characterize its clinicopathologic features and immunophenotypes, and discuss their implications in prognosis.
Methods
Tissue microarrays using samples from 85 ALCL patients were used to evaluate expression of c-MYC and anaplastic lymphoma kinase (ALK). c-MYC and ALK genetic alterations were detected using fluorescence in situ hybridization. The Kaplan–Meier and multivariate Cox regression methods were used for survival analysis.
Results
c-MYC was expressed in 24 of 85 samples (28.2%), and ALK was expressed in 54 (63.5%). c-MYC and ALK were co-expressed in 16 samples (18.8%). c-MYC expression and c-MYC and ALK co-expression increased with ALCL clinical stages and the International Prognostic Index (IPI) score (p < 0.05). Fifty of the samples (58.8%) had ALK rearrangement, and 18 (22.1%) had aneuploidy. c-MYC rearrangement was not detected, but aneuploidy was observed in 19 cases (22.4%). c-MYC aneuploidy was significantly different based on c-MYC expression and the IPI score (p < 0.05). c-MYC was a significant independent prognostic factor for progression-free survival and overall survival in patients with ALCL.
Conclusion
c-MYC protein expression and c-MYC aneuploidy could predict worse survival in patients with ALCL.
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Data availability
All data generated that are relevant to the results presented in this article are included in this article. Other data that were not relevant for the results presented here are available from the corresponding author (ZW Chen) upon reasonable request.
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Funding
This work was supported by the Natural Science Foundation of Shanxi Province (201801D121347, 201701D121165 and 2012011038-4) and the Intramural Research Program of Fenyang College of Shanxi Medical University (2016D10, 2016D12).
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Z.C. and F.C. designed the study. Z.C. and F.C. wrote the manuscript, and Z.C. revised the manuscript. Y.X. and Z.C. interpreted the results of the hematoxylin and eosin and immunochemical staining. F.C., Z.Z., and X.T. collected the clinical data and carried out immunochemical staining. F.C., Y.X., and S.L. performed TMA construction and FISH. F.C. and H.Z. were responsible for the statistical evaluation and analyzed data. All the authors have read and agreed to the published version of the manuscript.
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The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Medical Ethics Committee of Shanxi Tumor Hospital.
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Chen, Z., Chai, F., Xi, Y. et al. Aberrant expression and genetic alteration of c-MYC in anaplastic large cell lymphoma. J Cancer Res Clin Oncol 148, 267–278 (2022). https://doi.org/10.1007/s00432-021-03691-7
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DOI: https://doi.org/10.1007/s00432-021-03691-7