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Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method
Published on: September 10, 2017
p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated
1Department of AnesthesiaInstitut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. muret@igr.fr
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.
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