Biological roles and prognostic values of the epithelial-mesenchymal transition-mediating transcription factors Twist, ZEB1 and Slug in diffuse large B-cell lymphoma

Histopathology. 2013 Jan;62(2):326-33. doi: 10.1111/his.12000. Epub 2012 Nov 27.

Abstract

Aims: To evaluate the biological roles and prognostic significance of the epithelial-mesenchymal transition (EMT)-mediating transcription factors (TFs) Twist, ZEB1 and Slug in patients with diffuse large B-cell lymphoma (DLBCL). EMT has been shown to enhance solid tumour metastasis, invasion, and proliferation.

Methods and results: Expression of Twist, ZEB1 and Slug was evaluated immunohistochemically in eight samples from reactive lymphoid tissues and in diagnostic samples from 102 DLBCL patients treated with curative intent with R-CHOP-type chemotherapy. ZEB1 and Slug expression correlated with adverse disease presentation. However, cytoplasmic Slug expression was linked to a favourable disease outcome, whereas nuclear expression of ZEB1 indicated an adverse outcome.

Conclusions: This study shows that an EMT-like process occurs in lymphomas. Of the TFs investigated, ZEB1 seems to be the main one associated with adverse clinical presentation and clinical outcome. Surprisingly, Slug expression in cytoplasm was linked to a favourable prognosis. Further studies are needed to evaluate whether inhibition of ZEB1 could serve as a therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Epithelial-Mesenchymal Transition*
  • Finland / epidemiology
  • Homeodomain Proteins / metabolism*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / metabolism*
  • Prednisone / therapeutic use
  • Prognosis
  • Snail Family Transcription Factors
  • Survival Rate
  • Transcription Factors / metabolism*
  • Twist-Related Protein 1 / metabolism*
  • Vincristine / therapeutic use
  • Young Adult
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • Nuclear Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol