Publication Type
Journal Article
Version
publishedVersion
Publication Date
8-2000
Abstract
Disease stage at the time of diagnosis and response to therapy are the main prognostic factors for patients with Ewing sarcoma or peripheral neuroectodermal tumor (ES/PNET). The primary genetic alteration in ES/PNET, the fusion of the EWS gene with FLI1 or ERG, is diagnostically highly specific for these tumors, and molecular variation in the structure of the EWS-FLI1 fusion gene also is of prognostic significance. In contrast, secondary genetic alterations, such as P53 alterations, are relatively uncommon in ES/PNET, and their prognostic impact has not been extensively studied. METHODS: Prechemotherapy, paraffin embedded, nondecalcified, primary tumor material in a well-characterized series of 55 patients with ES/PNET with defined EWS-FLI1 fusion transcripts (32 patients with type 1 and 23 patients with other types) was studied retrospectively by immunohistochemical techniques for cell cycle regulators and proliferative markers, such as P53, P21(WAF1), and Ki-67, as well as by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique for apoptosis. Nuclear P53 expression in > 20% of tumor cells was scored as aberrant overexpression. Histologic response to neoadjuvant chemotherapy was assessed. RESULTS: Aberrant P53 expression (in > 20% of tumor cells) was present in 6 patients (11%) but showed no statistically significant correlation with disease stage, tumor size, proliferation rate (Ki-67), apoptotic rate (TUNEL), or EWS-FLI1 fusion type. By univariate analysis, the P53 > 20% group showed a significantly poorer overall survival among patients with localized disease (n = 43 patients) (P = 0.001) and in the entire study group (P = 0.01). In multivariate Cox analyses of overall survival, P53 > 20% was the strongest negative factor among prognostic factors available at the time of diagnosis (P = 0.001; relative risk [RR] = 9) and when chemotherapy response was included in the analysis (P53 > 20%: P = 0.01; RR = 10). CONCLUSIONS: P53 alteration appears to define a small clinical subset of patients with ES/PNET with a markedly poor outcome. The current observations warrant a systematic prospective study with comprehensive P53 mutation analysis. [See related article on pages 793-9, this issue.] Copyright 2000 American Cancer Society.
Keywords
bone tumor, translocation, point mutation, P21, Ki-67, chemotherapy response
Discipline
Econometrics | Medicine and Health Sciences
Research Areas
Econometrics
Publication
Cancer
Volume
89
Issue
4
First Page
783
Last Page
792
ISSN
0008-543X
Identifier
10.1002/1097-0142(20000815)89:4<783::aid-cncr10>3.0.co;2-q
Publisher
Wiley
Citation
De Alava, E.; Antonescu, C.; Panizo, A.; Leung, Denis H. Y.; Meyers, P.; Huvos, A.; Pardo-Mindan, F. J.; Healey, J.; and Ladanyi, M..
Prognostic Impact of P53 Status in Ewing Sarcoma. (2000). Cancer. 89, (4), 783-792.
Available at: https://ink.library.smu.edu.sg/soe_research/43
Copyright Owner and License
Publisher
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Additional URL
https://doi.org/10.1002/1097-0142(20000815)89:4<783::aid-cncr10>3.0.co;2-q