Prognostic impact of TP53 mutation status for adult patients with supratentorial World Health Organization Grade II astrocytoma or oligoastrocytoma: a long-term analysis.
BACKGROUND
The goal of the current study was to retrospectively assess the prognostic impact of TP53 mutation status and P53 expression/accumulation on long-term outcome for adult patients with supratentorial World Health Organization (WHO) Grade II astrocytoma or oligoastrocytoma.


METHODS
The authors revisited a previously published short-term data set containing information on 159 consecutive patients who were treated between 1991 and 1998. Each patient was screened for TP53 mutations and P53 overexpression/accumulation. The reference point for all analyses was the date of surgical treatment, and the date of last follow-up examination was August 2002. Overall survival, progression-free survival, postrecurrence survival, and time to malignant transformation were estimated using the Kaplan-Meier method, and potential prognostic factors were evaluated using the multivariate proportional hazards model.


RESULTS
The median follow-up duration for survivors was 80.4 months (standard deviation, 33.0 months). TP53 mutations, which were present in 49.1% of all tumors, occurred preferentially in gemistocytic tumors (P < 0.05). In addition, the TP53 status of the primary tumor was predictive of the TP53 status of the recurrent tumor in all cases of disease recurrence. The 5-year overall and progression-free survival rates were 77.5% and 43.2%, respectively, and the risk of malignant transformation at 5 years postsurgery was 32.7%. Unfavorable prognostic factors with respect to survival duration included older age (> or = 50 years; P < 0.002), gemistocytic subtype (P < 0.01), and positive TP53 mutation status (P < 0.05), all of which were also negatively associated with progression-free survival (P < 0.05, P < 0.001, and P < 0.003, respectively). In contrast, positive TP53 mutation status was the only significant predictor of a reduction in time to malignant transformation (P < 0.03). P53 overexpression/accumulation did not exhibit prognostic relevance in any of the multivariate models constructed in the current study.


CONCLUSIONS
TP53 mutations are common early events in the pathogenesis of WHO Grade II astrocytoma or oligoastrocytoma. In the current study, positive TP53 mutation status (but not P53 overexpression/accumulation) was found to be an independent unfavorable predictor of survival, progression-free survival, and time to malignant transformation. The therapeutic implications of these findings have yet to be determined.
Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
Marko
M
Ständer
Aurelia
A
Peraud
Barbara
B
Leroch
Friedrich W
FW
Kreth
D000328:Adult; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012189:Retrospective Studies; D015173:Supratentorial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014944:World Health Organization
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53