Oncogene expression in tumour cells of pediatric Hodgkin's disease in Argentina--correlation with Epstein Barr virus presence.
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.
Preciado
M V
MV
Laboratory of Virology, Ricardo Gutierrez Children's Hospital, Buenos Aires, Argentina.
Cristobal
E
E
Menarguez
J
J
Martinez Montero
J C
JC
Diez
B
B
De Matteo
E
E
Grinstein
S
S
D000293:Adolescent; D000956:Antigens, Viral / Q000378:metabolism; D001118:Argentina; D002648:Child; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism
D000956:Antigens, Viral; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2