Prognostic relevance of cell cycle regulating and apoptotic-related proteins in pediatric Hodgkin´s lymphomas

PAOLA ANDREA CHABAY; PESCE, P.; DE MATTEO, E; GARCIA LOMBARDI, M; STREITEMBERGER, P.; REY, G.; PRECIADO, M. V.

Oslo

Congreso; International Society of Pediatric Oncology Annual Meeting; 2004

Sociedad Internacional de Oncología Pediátrica

Background: Tumoral cells in Hodgkin lymphoma (HL) are germinal centre B-cell, that escape from apoptosis, implying a disturbance of the cell cycle and apoptosis regulation. This may involve abnormalities in specific cell cycle control genes, such as p53 and p21Waf1, and apoptosis related genes, such as p53 and bcl-2.  Objective:  to analyse p53,  p21Waf1 and bcl-2 expression and to correlate them with presenting clinical features and event free survival (EFS). Methods: Twenty-three cases of pediatric HL (13 mixed cellularity and 10 nodular sclerosis) from 1996 to 2002 were selected from the archives of the Pathology Service at Ricardo Gutierrez Children’s Hospital among N on the basis of available formalin-fixed paraffin-embedded lymph node biopsies. Patients were treated according to the CVPP-ABV protocol, the follow up media was 39 months. P53, bcl-2 and p21waf-1 proteins were assesed by immunohistochemistry using MoAbs by means of  a streptavidin-biotin complex-peroxidase detection system.  Results: patients’ age range was 4-17 years (median: 8) and the male:famale ratio was 3:1. Seventeen out of 23 (74%) shows EFS.  P53, p21Waf1 and bcl-2 proteins were detected in tumor cells in 65%, 74% and 35% on cases of HL respectively. Correlation of p53 and p21Waf1 staining revealed three patterns: I) p53+/ p21Waf1 + (15 cases), II) p53-/ p21Waf1 - (6 cases) and III) p53-/ p21Waf1 + (2 cases). Pattern I suggests wild type p53 protein able to induces the expression of p21Waf1 while pattern III suggests p53-independent p21Waf1 expression. These results are consistent with the interpretation that inactivating p53 gene mutations may be rare in HL. High expression of  p21Waf1 protein. All cases that expressed p21Waf1 correspond to patients presenting poor response to first line treatment and no EFS . P53 expression also denotes bad prognosis (RR:6). The p53+/ p21Waf1 + pattern is also related to a negative prognostic in these patients . Whereas, bcl-2 expression did not give prognostic information in our studied group. Conclusion: Survival chance depends on multiple biologic factors including alteration in the major tumor supresor pathways and cell-cycle checkpoints, that appears to determine the viability of malignants cells and consecuently the clinical outcome.