Overexpression of survivin in pediatric Hodgkin lymphoma tumor cells: Characterization of protein expression and splice-variants transcription profile

Exp Mol Pathol. 2019 Jun:108:24-31. doi: 10.1016/j.yexmp.2019.03.005. Epub 2019 Mar 12.

Abstract

Survivin is abundantly expressed during fetal development but absent in most differentiated adult tissues; an exception being components of the immune system, such as B and T lymphocytes. Beyond acting as a master regulator of the cell cycle, survivin acts as an inhibitor of apoptosis and is overexpressed in almost all carcinoma types; however, its expression in lymphomas is lesser-explored. Survivin's role in carcinogenesis was subjected to its sub-cellular localization and splice transcripts expression, namely wild-type survivin, survivin-∆Ex3 and survivin-2B. To assess survivin's expression and sub-cellular localization in Epstein Barr virus positive and negative biopsies from treatment naïve pediatric patients with Hodgkin lymphoma (HL), samples were stained for survivin protein by immunofluorescence. The proportion of survivin+ cells was calculated, survivin sub-cellular localization assessed and its fluorescence intensity quantified. Transcription profile of survivin mRNA variants was studied by RT-qPCR. Survivin was overexpressed in the nucleus of tumor cells, and also in a greater proportion of tumor cells, in comparison with the non-tumoral infiltrating cells. Although a higher expression of survivin was observed in advanced clinical stages, no correlation was found between the expression level of survivin and a proliferation marker, or event-free survival. Instead, survivin was related to apoptosis inhibition in tumor cells. Additionally, survivin's transcriptional variants displayed similar expression levels. Present results suggest that although survivin is overexpressed in Hodgkin's tumor cells, it may not play a central role in the progression of classic HL, or act as a suitable progression biomarker, as suggested for most carcinomas.

Keywords: Hodgkin lymphoma; Survivin; Survivin splice variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Splicing*
  • Survivin / genetics*
  • Survivin / metabolism

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Protein Isoforms
  • Survivin