POLIMORFISMO DO GENE TP53 EM SARCOMAS DE PARTES MOLES NO ADULTO

Abstract

Soft tissue sarcomas (STS) are tumors with mesodermical origin, comprising about 1% of all adult neoplasms. Because of its effect on the p53 protein coding sequence, and its association with an increased risk for some cancer types, TP53 codon 72 polymorphism has been investigated in several studies. TP53 codon 72 codes for either Arginine (p53Arg), or Proline (p53Pro) at the p53 protein primary sequence. It was demonstrated that such amino acid change affects p53 biochemical and biological properties, and several studies have been developed in order to associate TP53 codon 72 polymorphisms as a risk, and as a prognostic factor for different cancer types. Any published study on the TP53 codon 72 polymorphism in adult soft tissue sarcomas was found in the literature. The present study aimed to investigate TP53Arg/Pro polymorphism as a potential prognostic factor in 100 adult subjects with STS. Patients were assisted at the Hospital Araújo Jorge of the Associação de Combate ao Câncer em Goiás in Goiânia, Brazil. DNA from patients was obtained from formaldehyde-fixed and paraffin-embedded tissue samples stored at the Pathology Department of the institution. Control group included 85 healthy donors randomly selected from Goiânia s population and, for this group, DNA extraction was performed from peripheral blood. Polymorphism genotyping was achieved by using polymerase chain reaction (PCR) with specific primer sets for each polymorphic variant. Statistical analysis was performed by using GenePop Ò web version 3.4 software. In this study, TP53 allelic and genotypic frequencies were investigated for subjects and controls, however, any statistical difference between the two groups was found. Our study supports the evidence that p53Arg is the most frequent allele in Latin American population, but worldwide genic and genetic frequency data are conflicting because of ethnical differences among the studied populations. According to the results, no significant association was demonstrated between TP53 codon 72 polymorphism and clinocopathological characteristics such as gender, age, tumor localization, histology, tumor size, stage, grade, node status, and distant metastasis. The five-year overall survival for the study group was 48.1%. Tumors with p53Pro/Pro genotype demonstrated a reduced survival rate (30%) when compared to p53Arg/Arg (45%), and p53Arg/Pro group (54.9%), but this association was not statistically significant (p = 0.444). In the present study, the p53Arg variant was not statistically associated with a more favorable prognosis in adult STS patients.