C-MYC overexpression predicts aggressive transformation and a poor outcome in mucosa-associated lymphoid tissue lymphomas

Int J Clin Exp Pathol. 2014 Aug 15;7(9):5634-44. eCollection 2014.

Abstract

Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common, indolent B-cell lymphoma. MALT lymphoma with large tumor cells (LTCs) is believed to have the potential to transform to aggressive diffuse large B-cell lymphoma (DLBCL) which may have a poor prognosis. C-MYC is a transcription factor. Its translocation and overexpression predicts an inferior prognosis and poor response to therapy in cases of DLBCL. In the current study, C-MYC expression was detected in MALT lymphomas, and its relationship to the occurrence of LTCs, clinicopathological parameters and prognosis was assessed. A total of 69 cases were enrolled in the study, including 42 cases of MALT lymphoma without LTCs, 20 cases of MALT lymphoma with LTCs and 7 cases of DLBCL with a MALT lymphoma component (DLBCL+MALT). Immunohistochemistry and fluorescent in situ hybridization analyses were performed. In total, 15/42 (35.7%) cases were nuclear positive for C-MYC expression in the group without LTCs, whereas 15/20 (75.0%) and 4/7 (57.1%) cases were positive in the group with LTCs and in the group with DLBCL+MALT, respectively (P=0.004). Univariate and multivariate analysis were used to determine the correlations of C-MYC expression and clinicopathological parameters with overall survival (OS). C-MYC expression, Ann Arbor stage, LDH level and IPI were considerably associated with OS according to the univariate analysis. However, only C-MYC expression ≥ 20% showed a statistical significance in the multivariate analysis (HR=20.604, 95% CI: 1.909-222.412, P=0.013). Therefore, C-MYC overexpression may play an important role in aggressive transformation and is an independent prognostic factor in MALT lymphoma.

Keywords: C-MYC; MALT lymphoma; fluorescent in situ hybridization; immunohistochemistry; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Lymphoma, B-Cell, Marginal Zone / chemistry*
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / mortality
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoma, B-Cell, Marginal Zone / therapy
  • Lymphoma, Large B-Cell, Diffuse / chemistry*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-myc / analysis*
  • Proto-Oncogene Proteins c-myc / genetics
  • Risk Factors
  • Time Factors
  • Translocation, Genetic
  • Up-Regulation
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc