title: Prognostic value of Mdm2, p53 and p16 in patients with astrocytomas.
abstract: Surgical cure of gliomas infiltrating into the brain is practically impossible and their clinical course is primarily determined by the biological behavior of the tumor cell. The purpose of this study was to analyze retrospectively prognostic input of p53, Mouse double minute-2 (Mdm2) and p16 in 103 uniformly treated patients with astrocytic tumors. The expression of these molecules was measured by immunohistochemical procedure. Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5-122) months for the survivors. We observed that 66% of gliomas showed mutated p53, while only 17% overexpressed Mdm2, the p53-regulatory molecule. Besides, almost 50% of gliomas lost p16 immunopositivity. Only p53 labeling showed a positive correlation with the grade of malignancy, according with the WHO classification. The association between mutated p53 and histological grade remained when prognostic variables were considered in a multivariate analysis. No association between p53 status and overall survival was found. On the other hand, Mdm2 overexpression and, unexpectedly, p16 immunopositivity were associated with a shorter survival in an univariate analysis. However, Cox-regression analysis showed that only Mdm2 in female patients was an independent prognostic factor, associated with shorter survival. In conclusion, our results suggest that Mdm2 could be a relevant marker in determining the evolution of glioma patients and could provide a more objective way to classify astrocytomas.
authors.affiliation: Research Area of the Institute of Oncology Angel H. Roffo, Buenos Aires, Argentina.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Ranuncolo
authors.forename: Mirta
authors.initials: M
authors.lastname: Varela
authors.forename: Ana
authors.initials: A
authors.lastname: Morandi
authors.forename: José
authors.initials: J
authors.lastname: Lastiri
authors.forename: Silvia
authors.initials: S
authors.lastname: Christiansen
authors.forename: Elisa
authors.initials: E
authors.lastname: Bal de Kier Joffé
authors.forename: María G
authors.initials: MG
authors.lastname: Pallotta
authors.forename: Lydia
authors.initials: L
authors.lastname: Puricelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051736:Proto-Oncogene Proteins c-mdm2; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2