Aberrant expression and genetic alteration of c-MYC in anaplastic large cell lymphoma

J Cancer Res Clin Oncol. 2022 Jan;148(1):267-278. doi: 10.1007/s00432-021-03691-7. Epub 2021 Jun 16.

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.

Keywords: Anaplastic large cell lymphoma; Fluorescence in situ hybridization; Immunohistochemistry; Prognosis; c-MYC.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase / genetics*
  • Anaplastic Lymphoma Kinase / metabolism
  • Aneuploidy
  • Child
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Large-Cell, Anaplastic / genetics*
  • Lymphoma, Large-Cell, Anaplastic / mortality
  • Lymphoma, Large-Cell, Anaplastic / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Survival Analysis
  • Young Adult

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • ALK protein, human
  • Anaplastic Lymphoma Kinase