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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- 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