Influência da infecção por H. Pylori nas Vias Carcinogênicas Gástricas envolvendo os genes MYC e TP53

Abstract

Gastric cancer (GC) is the fifth most incident cancer and the fourth in mortality worldwide. The GC is extremely heterogeneous and among the molecules observed with alterations are the MYC and TP53 genes, involved with the cell cycle and apoptosis. Thus, the objective of this work was to investigate the relationship between the presence of H. pylori and the genotypes (cagA, cagE and vacA alleles), associated with the expression of TP53 and MYC. We studied 82 patients with GC. The presence of H. pylori and genotypes was performed using the PCR technique. MYC(+) overexpression and TP53(p53+) expression were detected by immunohistochemistry. H pylori infection was observed in 85.4% (70/82) of the cases, with vacAs1 being the most frequent genotype (87,1%; 61/70). The cagA and cagE genes were detected in 62.8% (44/70) and 54.3% (38/70) of cases, respectively. TP53(+) was detected in 28.6% (20/70), and MYC(+) at 36.6% (30/82) in the core; 6.1% (5/82) in the cytoplasm, and 7.3 (6/82) for co-localization. Comparative analyzes between the frequency of the genes studied or in combination showed that nuclear MYC positivity was significantly more frequent in diffuse tumors (50%; 18/36), showing approximately 2x risk of the MYC nuclear tumor developing the diffuse subtype [p=0.025; OR = 2.8 (1.01 - 7.96)]. In positive cases for H pylori, there was a risk tendency for the double-labelled MYCN(+)TP53(+) to develop the diffuse subtype [p=0.063; OR: 5.35 (0.63-65.33)]. In addition, cagA positive strains and the presence of nuclear MYC were significantly more frequent in diffuse tumors (10/17; 58,8%), were approximately 8x more likely to develop this subtype [p=0,006; OR = 8,21 (1,62 – 45,52)]. The results indicate that, in diffuse tumors, a carcinogenic pathway associated with TP53 expression, and possibly influenced by H pylori cagA(+), seems to occur probably through the MYC protein.