Polymorphisms in TPT1 Pathways in Pediatric Astrocytomas

Abstract

Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 (TPT1) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR, MDM2, TP53, and CDKN1A, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas (p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared (p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma (p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.

Keywords: MDM2; TCTP; TPT1; astrocytomas; biomarkers; polymorphisms.

Figure 1.

Immunoexpression for the five proteins TCTP, mTOR, MDM2, p53 and p21. Left column shows astrocytomas grade 1 and right column shows astrocytomas grade 4 (IHC, 200x).

Figure 2.

Survival and immunoexpression proteins (TCTP, MDM2, p53 and p21) distribution in glioblastomas (group 4). Survival was classified into two groups considering the mean of survival: below average survival (BAS) and above average survival (AAS). The proteins were evaluated according to the Allred value (distribution, intensity, Allred score). Each graphic has 3 analyses: 1 for distribution in below and above average survival; 2 for intensity in below and above average survival; 3 for Allred score in below and above average survival.