Avaliação imunoistoquímica de PI3K, PTEN e S6K1 em mucosas normais e displasias epiteliais orais

Abstract

Oral Potentially malignant disorders (OPMDs) enroll a set of conditions defined by the World Health Organization (WHO) as oral lesions that have been shown to be associated with an increased risk of malignant transformation. Sometimes, these lesions present oral epithelial dysplasia (OED) with different degrees, which can be predictors of malignancy. In this context, aiming to understand the process of progression of OPMDs, some cell signaling pathways have been studied. Among them, the phosphatidylinositol-3 kinase (PI3K) pathway stands out, which has key proteins such as PI3K and PTEN, involved in the activation and inhibition of the pathway, respectively, and S6K1, associated with increased protein synthesis and cell growth . Thus, the present study aimed to analyze the immunohistochemical expression of PI3K, PTEN and S6K1 in cases of OED and normal oral mucosa (NOM). The sample consisted of 20 cases of OED with different histological grades (8 low risk and 12 high risk) and 20 cases of NOM. Immunohistochemical verification was performed using anti-PI3K, anti-PTEN, anti-S6K1 antibodies. Categorical data were expressed in absolute frequency and compared by Fisher's exact test or Pearson's chi-square test, while continuous data were expressed as means ± SD of the calculated indices and histoscores, which were analyzed using the Mann-Whitney or Kruskal test -Wallis, followed by Dunn's post-test. The results showed a higher frequency of positive immunostaining for PI3K (95%) (p = 0.003) and S6K1 (100%) (p = 0.004) in OEDs, in addition to greater gain of nuclear PTEN (94.7%) (p = 0.002) and cytoplasmic (21.1%) (p = 0.03) in OEDs, compared to NOMs. In the binary system grading, a greater cytoplasmic gain of PTEN was observed in low-risk OEDs (44.4%) (p = 0.018), compared to high-risk ones. The calculated indices and histoscores were statistically higher for nuclear (5.83 ± 2.07) (p <0.001) and cytoplasmic PTEN (3.00 ± 1.91) (p <0.001) and for PI3K (93.00 ± 51.10) (p = 0.003) in OEDs, compared to NOMs, while for S6K1 no statistical difference was observed. The present study highlights the probable role of PI3K, PTEN and S6K1 proteins in the PI3K pathway, which suggest that the increased expression of these proteins may be associated with the development and progression of OED.