Prognostic impact of P53 status in Ewing sarcoma Journal Article
| Authors: | de Alava, E.; Antonescu, C. R.; Panizo, A.; Leung, D.; Meyers, P. A.; Huvos, A. G.; Pardo-Mindán, F. J.; Healey, J. H.; Ladanyi, M. |
| Article Title: | Prognostic impact of P53 status in Ewing sarcoma |
| Abstract: | BACKGROUND. 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. (C) 2000 American Cancer Society. |
| Keywords: | immunohistochemistry; adolescent; adult; cancer survival; child; controlled study; human tissue; treatment outcome; bone neoplasms; child, preschool; bone tumor; major clinical study; cisplatin; doxorubicin; antineoplastic agents; follow up; neoplasm staging; prospective studies; ki 67 antigen; reverse transcription polymerase chain reaction; apoptosis; gene expression; etoposide; tumor markers, biological; cyclophosphamide; vincristine; protein p53; ifosfamide; transcription factors; ewing sarcoma; rna; tumor suppressor gene; ki-67; oncogene proteins, fusion; tumor suppressor protein p53; bleomycin; point mutation; sarcoma, ewing's; protein p21; proto-oncogene protein c-fli-1; p21; translocation; chemotherapy response; humans; prognosis; human; male; female; priority journal; article |
| Journal Title: | Cancer |
| Volume: | 89 |
| Issue: | 4 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2000-08-15 |
| Start Page: | 783 |
| End Page: | 792 |
| Language: | English |
| DOI: | 10.1002/1097-0142(20000815)89:4<783::aid-cncr10>3.0.co;2-q |
| PUBMED: | 10951341 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work