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

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 ILPwith TNF-alpha andmelphalan 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.