Article: article from journal or magazin.
p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.
Annals of Oncology
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.
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
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