Oncogene expression in tumour cells of pediatric Hodgkin's disease in Argentina--correlation with Epstein Barr virus presence

Pathol Res Pract. 1998;194(1):25-31. doi: 10.1016/s0344-0338(98)80008-3.

Abstract

A new category of oncogenes regulating apoptosis, p53 and bcl-2, and the Epstein Barr virus (EBV) latent membrane protein-1 (LMP-1) have been related to Hodgkin's disease (HD) pathogenesis. We attempt to determine p53, mdm2, p21waf-1, bcl-2 and LMP-1 immunohistochemical expression in tissue sections from formalin-fixed, paraffin-embedded lymph node biopsies of pediatric HD. P53 was detected in the nucleus of Reed Sternberg cells and their variants (H-RS) in 68% of the HD cases. However, there was no statistically significant association with either clinical stages or with histological subtypes. P21waf-1, an indirect marker of p53 functional status, showed nuclear labelling of H-RS in all the studied cases. MDM2 co-expressed with p53 in 62% of the cases, suggesting that both proteins regulate one another, in HD by a self regulatory loop. Bcl-2 cytoplasmatic expression in H-RS was demonstrated in 65% of the cases. There was co-expression of bcl-2 and p53 in 51%, but it failed to correlate with a poor prognosis. LMP-1 labelling was shown in 51% of the cases, disclosing a statistically significant association with the under 6-year group (p = 0.005, Fisher's exact test). Since LMP-1 induces the expression of bcl-2 in vitro, the relation of both proteins was analysed and found to co-express in 15/37 cases, with a statistically significant association only in the under 6-year group (p = 0.001, Fisher's exact test). Abnormal accumulation of these oncoproteins in tumour cells could play a role in the pathogenesis of a subset of pediatric HD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, Viral / metabolism
  • Argentina
  • Child
  • Child, Preschool
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Female
  • Herpesvirus 4, Human / physiology*
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology
  • Hodgkin Disease / virology*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Infant
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymph Nodes / virology
  • Male
  • Nuclear Proteins*
  • Oncogene Proteins, Viral / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-mdm2
  • Tumor Suppressor Protein p53 / metabolism
  • Viral Matrix Proteins / metabolism

Substances

  • Antigens, Viral
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Nuclear Proteins
  • Oncogene Proteins, Viral
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Viral Matrix Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2