EXPRESSION OF RETINOBLASTOMA GENE-PRODUCT AND P21 (WAF1 CIP-1) PROTEIN IN GLIOMAS - CORRELATIONS WITH PROLIFERATION MARKERS, P53 EXPRESSIONAND SURVIVAL/

Using immunohistochemistry we evaluated the expression of two negative regulators of the cell cycle, the retinoblastoma gene product (pRb) a nd the WAF1/Cip1 gene product (p21), in consecutive paraffin sections from 54 gliomas (49 astrocytomas and 5 oligodendrogliomas) and related it to clinicopathological parameters, proliferative fraction, p53 exp ression and survival. Survival analysis was restricted to the group of diffuse astrocytomas (48 patients). pRb expression did not correlate with histological type, grade or p53 expression, while a moderately st rong correlation existed between pRb expression and the percentages of proliferating cell nuclear antigen (PCNA) and MIB-1-positive cells. I n 30% of cases we observed diminished pRb expression (i.e., a low pRb/ Ki-67 ratio), irrespective of grade or histological type. p21 protein was elevated in 50% of cases, especially within the higher grades. The percentage of p21-positive cells was not related to histological type or grade but correlated loosely with PCNA and pRb expression. A p53-n egative/p21-negative phenotype was characteristic of oligodendroglioma s and low-grade astrocytomas, whereas the p53-positive/p21-positive, p 53-positive/p21-negative and p53-negative/p21-positive phenotypes were almost equally distributed among high-grade tumors. In survival analy sis (either univariate or multivariate) diminished pRb expression was not a statistically significant prognostic indicator. In contrast, p21 expression emerged as an important indicator of shortened disease-fre e survival, in both univariate and multivariate analyses. Moreover, th e double-positive p53/p21 phenotype tended to be associated with a sho rter overall survival. Our results suggest that Rb gene deregulation d oes not significantly affect prognosis but p21 expression may play an important role in disease-free survival of astrocytoma patients.