TP53 Mutations and Chemotherapy Response to Neoadjuvant Metotrexate, Cisplatin and Adryamicin Chemotherapy in Resected Osteosarcoma

Osteosarcoma is a rare and highly malignant tumor that usually affects adolescents and young adults. Despite current management protocols, up to half of patients succumb to the disease. Moreover, there is no well-characterized molecular marker for diagnosis and prognosis. TP53 alterations have been associated with a poor prognosis in many cancers. The aim of this retrospective work was to find out whether TP53 functional status predicts response to neoadjuvant chemotherapy and thus may help treatment decision for osteosarcoma patients. Seventeen biopsies of osteosarcoma patients receiving primary metotrexate, cisplatin and adryamicin chemotherapy followed by surgery were analyzed. TP53 exons 5-9 mutations were screened. Among 17 biopsies, 4 (23.5%) displayed TP53 mutations: 3 deletions and one single-nucleotide substitution. The presence of TP53 gene mutation does not correlate with resistance to chemotherapy according to histological Rosen grade and nevertheless is associated with patient’s age in a significant manner (p < 0.05). The presence of non-mutated TP53 is not entirely specific for a good prognosis. We found no evidence that TP53 mutations predict chemoresistance in osteosarcoma patients more over the overall survival curve, followed for more than 12 years, showing no difference between patients with tumors harboring wild type or mutated TP53 gene (p < 0.5). Further analysis to identify other genes that can influence chemotherapy response and clinical outcome in osteosarcoma is needed to improve patient treatment.