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

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.

In: Annals of Oncology, 2007, vol. 19, no. 4, p. 793-800

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    Title
    • p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-α and melphalan
    Author
    • Muret, J.. Department of Anesthesia
    • Yacoub, M.. Department of Pathology
    • Terrier, P.. Department of Pathology
    • Drusch, F.. Laboratoire de Recherche Translationnelle, Module d'Histocytopathologie
    • Laplanche, A.. Department of Public Health
    • Gaudin, C.. Institut National de la Santé et de la Recherche Médicale U753 Unit, Immunologie des Tumeurs Humaines: Interaction Effecteurs Cytotoxiques-système Tumoral, Institut Gustave-Roussy, Villejuif Cedex, France
    • Richon, C.. Institut National de la Santé et de la Recherche Médicale U753 Unit, Immunologie des Tumeurs Humaines: Interaction Effecteurs Cytotoxiques-système Tumoral, Institut Gustave-Roussy, Villejuif Cedex, France
    • Le Péchoux, C.. Department of Radiotherapy
    • Le Cesne, A.. Department of Medical Oncology
    • Lejeune, F. J.. Multidisciplinary Oncology Centre, Centre Pluridisciplinaire d'Oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
    • Tursz, T.. Department of Medical Oncology
    • Fouret, P.. Department of Pathology
    • Bonvalot, S.. Department of Surgery
    • Chouaib, S.. Institut National de la Santé et de la Recherche Médicale U753 Unit, Immunologie des Tumeurs Humaines: Interaction Effecteurs Cytotoxiques-système Tumoral, Institut Gustave-Roussy, Villejuif Cedex, France
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Annals of Oncology, 2007, vol. 19, no. 4, p. 793-800. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:298928
    Summary
    Background: Recombinant tumor necrosis factor-α (TNF-α) 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-α and loss of p53 function contributes to the resistance of tumour cells to TNF-α. The relationship between p53 status and response to TNF-α 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-α 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-α and melphalan response in clinical use