Expression level of the mutant gene p53 in osteosarcoma and its role in the efficacy of treatment

It is believed that the main factors determining the prognosis of cancer are the prevalence and degree of differentiation of the tumor. In recent years, more and more attention has been paid to genetic factors that determine the individual risk of developing cancer, as well as participate in the processes of carcinogenesis in general. Therefore, the study of molecular-biological tumor markers, which are specific indicators of the high risk of tumor progression and the relationship to treatment efficacy, has acquired clinical significance. Objective. To study the effectiveness of treatment of patients with osteosarcoma depending on the change in expression of the p53 gene. Materials and methods. Under supervision were 221 patients with osteosarcoma. Patients received various types of treatment. Neoadjuvant polychemotherapy (PCT) was performed in 184 (83,2%) patients, of which 131 (71,2%) patients underwent systemic neoadjuvant CT, and 29 (15,7%) patients underwent prolonged intra-arterial regional chemotherapy (PIRC). A combination of systemic PCT and PIRC was performed by 24 (13%) patients. Immunohistochemistry (IHC) was performed by avidin-biotin-peroxidase test using primary antibodies (Dako, Novocastra™) to mp53 as a gold standard procedure. Results. Analysis of the obtained data allow establishing that expression and overexpression of mtp53+ occurs in patients with osteosarcoma with a low degree of tumor differentiation (G₃) 9 times more often. In patients with stage 3 and 4 clinical stages of osteosarcoma, the positive response of mtp53+ was 4-fold higher compared to patients with 1-2 stages. Achievement of complete morphological regression during IHC was revealed in 13% of patients, among them in 70,6% of patients the expression of mutant p53 gene was absent. At 15,7% after the use of the PIRC scheme, complete morphological regression was observed, in 87,5% of these patients the mutant p53 gene was also absent. The conclusion. High and average expression of the mutant p53 gene in patients with OS has an associative relationship with a low degree of tumor differentiation (G₃) with stages 3 and 4 of the tumor process, with a large tumor size, low therapeutic pathomorphism (1 and 2), with a chondroblastic histological variant and osteolytic radiological form. The decrease in the timing of relapses, distant metastases and life expectancy in patients with mild and high expression of the mtp53 gene was found, regardless of the therapy.

osteosarcoma, polychemotherapy, mtp53 gene, survival and risk function