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

J. Muret, M. Yacoub, P. Terrier, F. Drusch, A. Laplanche, C. Gaudin, C. Richon, C. Le Péchoux, A. Le Cesne, F. J. Lejeune, T. Tursz, P. Fouret, S. Bonvalot, S. Chouaib

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    Abstract

    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 bea clue to a role of p53 protein status in TNF-α and melphalan response in clinical use.

    Original languageEnglish
    Pages (from-to)793-800
    Number of pages8
    JournalAnnals of Oncology
    Volume19
    Issue number4
    DOIs
    Publication statusPublished - 1 Jan 2008

    Keywords

    • Isolated limb perfusion
    • Limb sarcoma
    • Melphalan
    • P53 status
    • Tumour necrosis factor-alpha

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