p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.

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Ressource 1Download: serval:BIB_C333B2CBD99E.P001 (970.98 [Ko])
State: Public
Version: author
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Serval ID
serval:BIB_C333B2CBD99E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.
Journal
Annals of Oncology
Author(s)
Muret J., Yacoub M., Terrier P., Drusch F., Laplanche A., Gaudin C., Richon C., Le Péchoux C., Le Cesne A., Lejeune F.J., Tursz T., Fouret P., Bonvalot S., Chouaib S.
ISSN
1569-8041[electronic]
Publication state
Published
Issued date
2008
Volume
19
Number
4
Pages
793-800
Language
english
Abstract
BACKGROUND: Recombinant tumor necrosis factor-alpha (TNF-alpha) combined to melphalan is clinically administered through isolated limb perfusion (ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha and loss of p53 function contributes to the resistance of tumour cells to TNF-alpha. The relationship between p53 status and response to TNF-alpha and melphalan in patients undergoing ILP is unknown. PATIENTS AND METHODS: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N-terminal region of both the wild-type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters. RESULTS: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILP with TNF-alpha and melphalan showed significantly higher levels of p53-mutated protein. CONCLUSIONS: Our results might be a clue to a role of p53 protein status in TNF-alpha and melphalan response in clinical use.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Chemotherapy, Cancer, Regional Perfusion, Child, Disease-Free Survival, Female, Humans, Immunohistochemistry, Kaplan-Meiers Estimate, Magnetic Resonance Imaging, Male, Melphalan/administration & dosage, Middle Aged, Mutation, Missense, Sarcoma/chemistry, Sarcoma/drug therapy, Treatment Outcome, Tumor Markers, Biological/analysis, Tumor Markers, Biological/immunology, Tumor Necrosis Factor-alpha/administration & dosage, Tumor Suppressor Protein p53/analysis, Tumor Suppressor Protein p53/genetics
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2009 12:59
Last modification date
25/09/2019 7:10
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