PROGNOSTIC RELEVANCE OF CELL CYCLE REGULATING

PESCE P; CHABAY P; DE MATTEO E; STEITEMBERGER P; REY G; PRECIADO MV

Oslo, Noruega

Congreso; 36th CONGRESS OF THE INTERNATIONAL SOCIETY OF PAEDIATRIC ONCOLOGY; 2004

INTERNATIONAL SOCIETY OF PAEDIATRIC ONCOLOGY

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 p21 Waf1, and apoptosis related genes, such as p53 and bcl-2.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 p21 Waf1, 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).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 23 on the basis of available formalin-fixed paraffin-embedded lymph node biopsies. Patients were treated according to the CVPP-ABV protocol. P53, bcl-2 and p21waf-1 proteins were assesed by immunohistochemistry.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 23 on the basis of available formalin-fixed paraffin-embedded lymph node biopsies. Patients were treated according to the CVPP-ABV protocol. P53, bcl-2 and p21waf-1 proteins were assesed by immunohistochemistry. Results. patients’ age range was 4–17 years (median: 8) and the male:famale ratio was 3:1. EFS was 74% (16/23). 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) p53þ/ p21Waf1 þ (15 cases), II) p53-/ p21Waf1—(6 cases) and III) p53-/ p21Waf1 þ (2 cases). All relapsed in patiens ocurred with Pattern 1 (6/15 cases) (P:<0.1). 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.patients’ age range was 4–17 years (median: 8) and the male:famale ratio was 3:1. EFS was 74% (16/23). 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) p53þ/ p21Waf1 þ (15 cases), II) p53-/ p21Waf1—(6 cases) and III) p53-/ p21Waf1 þ (2 cases). All relapsed in patiens ocurred with Pattern 1 (6/15 cases) (P:<0.1). 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.þ/ p21Waf1 þ (15 cases), II) p53-/ p21Waf1—(6 cases) and III) p53-/ p21Waf1 þ (2 cases). All relapsed in patiens ocurred with Pattern 1 (6/15 cases) (P:<0.1). 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.þ (2 cases). All relapsed in patiens ocurred with Pattern 1 (6/15 cases) (P:<0.1). 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.P:<0.1). 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. 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.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.