Document Detail

Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse.
MedLine Citation:
PMID:  15659501     Owner:  NLM     Status:  MEDLINE    
PURPOSE: EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES.
PATIENTS AND METHODS: We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively.
RESULTS: Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases.
CONCLUSION: Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse.
Hsuan-Ying Huang; Peter B Illei; Zhiquan Zhao; Madhu Mazumdar; Andrew G Huvos; John H Healey; Leonard H Wexler; Richard Gorlick; Paul Meyers; Marc Ladanyi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  23     ISSN:  0732-183X     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-20     Completed Date:  2005-03-11     Revised Date:  2011-06-09    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  548-58     Citation Subset:  IM    
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
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MeSH Terms
Bone Neoplasms / drug therapy*,  genetics*,  pathology
Child, Preschool
DNA Mutational Analysis
Follow-Up Studies
Genes, p16*
Genes, p53*
In Situ Hybridization, Fluorescence
Middle Aged
Neoplasm Staging
Oncogene Proteins, Fusion / genetics*
Proto-Oncogene Protein c-fli-1
Sarcoma, Ewing's / drug therapy*,  genetics*,  pathology
Sequence Deletion
Survival Analysis
Transcription Factors / genetics*
Treatment Outcome
Tumor Suppressor Protein p14ARF / genetics*
Reg. No./Substance:
0/EWS-FLI fusion protein; 0/Oncogene Proteins, Fusion; 0/Proto-Oncogene Protein c-fli-1; 0/Transcription Factors; 0/Tumor Suppressor Protein p14ARF

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