Overexpression of p53 protein in primary Ewing’s sarcoma of bone: relationship to tumour stage, response and prognosis

Abstract

Summary Biopsy tissues of 52 patients with Ewing's sarcoma of bone treated between 1983 and 1993 were examined immunohistochemically to determine the significance of p53 protein in diagnosis and prognosis of Ewing's sarcoma. Mean age at diagnosis was 17 years (range 6-36) and minimum follow-up was 30 months. The tumours were located in the extremities and central bones in 35 and 17 patients respectively. Metastases were present in seven patients at diagnosis. Treatment consisted of chemotherapy, surgery and/or radiotherapy in all the patients. Overexpression of p53 protein was demonstrated in seven patients (14%). There was no relationship between expression of p53 and site of tumours. Patients who overexpressed p53 protein appeared to have more advanced diseases at diagnosis and poorer response to chemotherapy than those without p53 overexpression. The 5-year relapse-free survival and overall survival in patients without metastases at the time of diagnosis were 66% and 71%, respectively, in p53 protein-negative patients compared with 20% relapsefree and overall survival in those with p53 protein overexpression (P = 0.01). The poorer prognosis in p53 protein-positive patients was independent of site, local treatment or necrosis of the tumours (P < 0.05). Over-expression of p53 protein is an independent poor prognostic factor in Ewing's sarcoma of bone.

Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics

“…Coexpression of Sp1 with EWS-ets oncoprotein enhances activation of vascular endothelial growth factor, the expression of which was shown to be a negative predictor of survival in Ewing's sarcoma (43). Aberrations in p53 were found in f10% of Ewing's sarcoma cases and were associated with shorter survival (44,45). Taken together, these observations suggest that nucleophosmin can be a single biomarker probably by linking these functionally different proteins.…”

Nutlin-3a Is a Potential Therapeutic for Ewing Sarcoma

“…The molecular alterations that abrogate the tumor surveillance role of p53 during the development of Ewing sarcoma are largely unknown, with infrequent reports of CDKN2A (p14 ARF ) deletion and of MDM2 amplification occurring in only 20% and 10% of all ESFT cases, respectively (5,6). The importance of p53 pathway integrity in ESFT is clearly showed by observations that the minority of ESFTs with TP53 mutations or CDKN2A deletions are associated with reduced chemoresponse and markedly poorer outcomes (7)(8)(9).…”

Prognostic significance of p16INK4a alteration for Ewing sarcoma

“…Recent studies have indicated the presence of the p53 gene alteration in 4% to 13% of patients [17][18][19][20][21][22][23] and the p16 INK4a gene alteration in 12% to 26% of patients [23][24][25][26][27][28][29] with Ewing sarcoma. These data indicated the presence of the p53 gene alteration among 11% of patients, the p16 INK4a gene alteration among 17%, and either alteration among 24% of patients.…”

“…[17][18][19][20][21][22][23][24][25][26][27][28][29] It has been suggested that the presence of these alterations potentially is linked with a poor prognosis for patients with this disease. [21][22][23]27,29 In addition, the presence of metastasis at diagnosis defines an advanced stage of the disease and has been considered the most unfavorable prognostic factor. 30 However, there have been discrepancies in the observed associations between p16…”