Prognostic implications of p53 overexpression in supratentorial astrocytic tumors.
The wild-type p53 gene is thought to play a critical role in tumor suppression and has been shown to reverse the transformed phenotype of tumor cells in vitro. Mutational inactivation of this aspect of p53 activity occurs frequently in many human neoplasms, including astrocytomas, and is thought to represent a critical step in tumor progression. We have found previously that the presence of p53 immunoreactivity was significantly associated with malignant astrocytomas arising in younger patients, although occurring infrequently in tumors in older patients. Given that young age is the most consistent clinical factor predictive of longer survival in patients with astrocytomas, this suggested that p53 protein accumulation might be a molecular predictor of enhanced survival. To test this hypothesis, we retrospectively studied the association of p53 overexpression with survival in 149 patients with astrocytomas, using univariate and multivariate analysis to determine its value in predicting survival. Although our analysis reaffirmed the strong association between young age and increased survival, we were unable to demonstrate any difference in survival between patients with Grade III and IV tumors with p53 immunoreactivity compared with those without. Presumably, once a tumor has progressed to high grade, the relative importance of p53 status as a predictor of survival is low, probably because of the large number of accumulated genetic alterations associated with malignant tumors. In contrast, the presence of p53 overexpression in Grade II astrocytomas seemed from survival curves to indicate shorter survival compared with patients who had no p53 immunoreactivity. However, this variable did not quite reach statistical significance (P = 0.08) as an independent predictive variable in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Clinical Neuroscience, Brown University, Rhode Island.
B S
BS
Chozick
J C
JC
Pezzullo
M H
MH
Epstein
P W
PW
Finch
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D001921:Brain / Q000473:pathology; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D015173:Supratentorial Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53