Expression of FoxO3a in clinical cases of malignant lymphoma

Pathol Res Pract. 2013 Nov;209(11):716-20. doi: 10.1016/j.prp.2013.08.003. Epub 2013 Aug 14.

Abstract

Cancer-initiating cells (CICs) are a limited number of cells with tumorigenic activity. Few studies have been performed on CICs in malignant lymphoma. We recently demonstrated that a small number of FoxO3a-expressing cells possessed CIC-like potential in Hodgkin's lymphoma (HL) cell lines. In the present study, FoxO3a expression was examined immunohistochemically in 137 patients with malignant lymphoma. Among patients with HL, FoxO3a-positive tumor cells were detected in 11 of 11 with nodular sclerosis classical HL, 8 of 15 with mixed cellularity classical HL, 0 of 1 with lymphocyte-rich classical HL, and 2 of 3 with nodular lymphocyte-predominant HL. Only limited numbers of patients with non-HL expressed FoxO3a: 4 of 66 with diffuse large B-cell lymphoma, 1 of 20 with follicular lymphoma, and 1 of 5 with peripheral T-cell lymphoma, not otherwise specified. No FoxO3a expression was detected in patients with mantle cell lymphoma (n=3), extranodal marginal zone B-cell lymphoma (n=3), mediastinal large B-cell lymphoma (n=1), NK/T cell lymphoma (n=5), anaplastic large cell lymphoma (n=2), or T-lymphoblastic lymphoma/leukemia (n=2). These results suggest that FoxO3a is expressed mostly in patients with HL, but not in patients with non-HL. FoxO3a expression was limited to a small number of Hodgkin cells in a quiescent state. FoxO3a may be a CIC marker of HL, but not of non-HL.

Keywords: Cancer initiating cells; FoxO3a; Malignant lymphoma.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Cellular Senescence
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / analysis*
  • Hodgkin Disease / metabolism*
  • Hodgkin Disease / pathology
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lymphoma, Non-Hodgkin / chemistry
  • Lymphoma, Non-Hodgkin / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / analysis

Substances

  • Biomarkers, Tumor
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-akt