Prognostic impact of TP53 mutations and P53 protein overexpression in supratentorial WHO grade II astrocytomas and oligoastrocytomas.
OBJECTIVE
The purpose of this study was to analyze retrospectively timing, frequency, and prognostic impact of TP53 mutations and P53 protein accumulation in supratentorial WHO grade II astrocytomas and oligoastrocytomas of adult patients.


METHODS
We included 159 consecutively treated patients (1991-1998), and each tumor was screened for TP53 mutations and P53 protein overexpression. Prognostic evaluation was performed with the multivariate proportional hazards model.


RESULTS
TP53 mutations (P53 protein overexpression) were detected in 49% (47%) of all tumors with a preference for the gemistocytic subtype (P < 0.05). The TP53 status of the primary tumor was predictive for the status of the recurrent tumor, and tumor recurrence/progression was associated with an increase of P53 immunopositive cells in 68% of the investigated tumors. Univariately, gemistocytic subtype and presence of TP53 mutation (but not P53 accumulation) were unfavorable predictors for progression-free survival (P < 0.05); multivariately, only the gemistocytic subtype remained unfavorable influence (P = 0.04). No overall prognostic impact of the TP53 status on survival and time to malignancy was observed (P < 0.05). Five nongemistocytic tumors with a codon 175 TP53 mutation exhibited a significantly worse prognosis as compared with those with any other mutational sites (5-year progression-free survival: 0%; 5-year malignant transformation: 100%; P < 0.001).


CONCLUSIONS
TP53 mutations are frequent and early events in the pathogenesis of WHO grade II astrocytomas/oligoastrocytomas, and most of the univariately detected overall prognostic impact of the TP53 status must be related to the influence of the gemistocytic subtype. In nongemistocytic astrocytomas, a hot spot codon 175 TP53 mutation indicates a worse prognosis in terms of time to progression and malignancy.
Peraud
Aurelia
A
Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany 81377. Aurelia.Peraud@helios.med.uni-muenchen.de
Kreth
Friedrich W
FW
Wiestler
Otmar D
OD
Kleihues
Paul
P
Reulen
Hans-Jürgen
HJ
D000328:Adult; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012720:Severity of Illness Index; D015173:Supratentorial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D014944:World Health Organization
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53