Análise imunoistoquímica de marcadores da via de sinalização Wnt (Wnt10b e β-catenina) em displasia epitelial oral

Abstract

Introduction: The molecular mechanisms responsible for the progression of Oral Potentially Malignant Disorders (OPMDs) to oral cancer remain poorly understood. Evidence points to the relevance of the Wnt/β-catenin signaling pathway in the progression of Oral Epithelial Dysplasia (OED) to Oral Squamous Cell Carcinoma (OSCC). Objective: To evaluate the immunoexpression of Wnt10b and β-Catenin in a series of cases of OED and Tongue Squamous Cell Carcinoma (TSCC), relating it to clinical and morphological parameters. Materials and Methods: The sample consisted of 20 cases of hyperkeratosis, 50 cases of OED, and 20 cases of TSCC. Clinical parameters regarding the patient (sex, age) and lesions (anatomical location and clinical staging-TNM) were considered. For the morphological analysis of OEDs, we considered the binary and WHO (2022) classification, and for TSCC, the WHO (2022) classification. For the immunohistochemical study, primary anti-β-Catenin and anti-Wnt10b antibodies were used, and the analysis was performed quantitatively, considering epithelial cells with brown membrane, cytoplasm, and/or nucleus as positive. Normal Oral Mucosa (NOM) cases were used as the control group. In the statistical analysis, Mann-Whitney and Kruskal-Wallis tests were used, with a p-value <0.05. Results: Greater cytoplasmic staining of Wnt10b (Mean=39.0; p=0.008) and β-Catenin (Mean=54.8; p=0.006) was observed in TSCC compared to NOM and OED, respectively. There was greater nuclear/cytoplasmic staining of Wnt10b (Mean=52.7) in moderate OED compared to mild OED and hyperkeratosis (p<0.001). β-Catenin showed greater nuclear/cytoplasmic staining in severe OED (Mean=7.2; p=0.001). In the binary classification, high-risk OED cases exhibited greater nuclear/cytoplasmic staining of Wnt10b (Mean=41.0) and β-Catenin (Mean=4.5) (p<0.001) than low-risk cases. There was a positive correlation between the histological grade of OED and nuclear/cytoplasmic staining levels of Wnt10b and β-Catenin (Rho=0.467, Rho=0.594, p<0.001, respectively). A significant association was observed between cytoplasmic staining of β-Catenin and TSCC cases in clinical stage III/IV (p=0.029). There was a positive correlation between clinical staging and cytoplasmic immunoexpression of β-Catenin (Rho=0.456, p<0.05). Conclusions: We observed an increase in the expression of Wnt10b and β-Catenin proteins as the histopathological grade of OED increased. Therefore, our results suggest the involvement of these proteins in epithelial dysplasia progression.