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.

HMGA1 expression in human gliomas and its correlation with tumor proliferation, invasion and angiogenesis

“…Malignant glioma is the most common central nervous system (CNS) tumor, and mortality is extremely high [1,2]. Despite optimum treatment, median survival is only 12-15 months for patients with glioblastoma multiforme (GB), 2-3 years for patients with anaplastic astrocytoma (AA, WHO grade III), and 5-10 years for patients with diffuse astrocytoma (DA, WHO grade II) [3].…”

Effects of the single nucleotide polymorphism at MDM2 309 on breast cancer patients with/without BRCA1/2 mutations

“…Several studies have found negative correlations between MDM2 tumor expression and prognosis in various cancers including breast, ovarian and brain [7-9]. Two studies have also noted a negative effect of MDM2 SNP309 G/G on survival of patients with metastatic gastric and renal cell cancer[10,11].…”

Correlation analysis between the expression of P21WAF1/CIP1, P16 proteins and human glioma

“…Unfortunately, surgical cure, as the basic treatment of malignant gliomas, is rare, as it is practically impossible to resect effectively beyond the limits of a macroscopically visible tumour without drastically compromising neurologic function. As a result, gliomas have a poor prognosis [3,4]. In order to resolve this problem, many investigations have been performed and recent discoveries have shed light on the molecular events which deregulate the cell cycle in brain tumours.…”