Avaliação da expressão gênica e proteica da via de sinalização WNT/β-catenin em amostras de leucoplasia bucal e sua relação com fatores prognósticos com ênfase na transformação maligna

Abstract

Oral leukoplakia (LB) is the main precancerous lesions of the oral cavity. The diagnosis must be confirmed by histological findings, to exclude any alteration of the oral mucosa and verify signs of malignancy, as well as gradations of epithelial dysplasia. The WNT/β-catenin pathway comprise the regulation of a wide variety of physiological processes in different species, with a decisive role in embryonic development, cell proliferation and differentiation. Alterations in components of this pathway have also been reported in neoplasms of the oral cavity and precancerous disorders of oral mucosa. The objective of this study was to identify the pattern of gene transcription (functional expression) belonging to the signaling pathway WNT/β-catenin and their relationship with their gene products in a tissue sample of LB and its relationship with clinicopathological factors considered markers of malignant transformation. For this purpose, a sample of LB was selected in patients treated at the oral diagnosis department (FOUFU) from 1994 to 2014. The evaluation of gene and protein expression were performed by qPCR and immunohistochemistry method respectively. Most patients belonged to males (53.8%) and had a median age of 56 years, ranging from 34-93 years. Most of the patients were smokers and the place most affected was the cheek. Approximately 75% of patients had LBR and in six cases was evidenced malignant transformation of the lesion. Initial lesion size was a factor associated with an increased risk of malignant transformation. Overall, the relative expression of all genes was higher in the control group than in the group LB. It was found higher protein expression of WNT 1, β-catenin, c-Myc, CiclinD1 in normal mucosa than in group LB. For GSK3β, APC and E-cadherin was higher expression in the LB group than in the control group. The smoking cessation offers better prognosis for the patient, reflecting a clinical and histologic improvement of LB. In conclusion, the present study showed that a reduction in the expression of CCNTB1, CDH1 and APC may be a critical event in the progression and malignant transformation of LB and increased CCND1 expression in LAR can be considered a prognosis worsening factor of this disease.