Avaliação molecular e imuno-histoquímica de malformações linfáticas orais

Abstract

Lymphatic malformations are developmental disorders characterized by excessive growth of lymphatic vessels. This condition occurs mainly in the head and neck region due to the physiological presence of high concentration of lymphatic vessels in the region. Lymphatic malformations may occur in isolation or associated with syndromes such as CLOVES and Klippel-Trènaunay. Mutations in the PIK3CA gene and activation of the PI3K/AKT and MAPK/ERK pathways may occur both in sporadic lymphatic malformations and in those associated with syndromes. Mutations in hotspot 1047 are the most frequently found in isolated lymphatic malformation. However, in oral lymphatic malformations it is not known whether these mutations occur. The aim of this study was to evaluate the presence of mutations in codon 1047 of the PIK3CA gene and to evaluate the activation of PI3K/AKT and MAPK/ERK pathways in samples of oral lymphatic malformations. A convenience sample of 14 tissues of oral lymphatic malformations formalin fixed paraffin embedded were submitted to immunohistochemistry reactions to the phosphorylated forms of AKT1 (pAKT-Ser473) and ERK1/2 (pERK1/2-Thr202/Tyr204), activation markers of PI3K/AKT and MAPK/ERK pathways, respectively. Four of these samples were submitted to Sanger Sequencing for codon 1047 of the PIK3CA gene. Positive marking patterns for pAKT1 and pERK1/2 were observed in the endothelial cells of all samples of oral lymphatic malformations evaluated. All samples submitted to Sanger Sequencing were wild type for the region of interest. With the results obtained it is suggested that the PI3K/AKT and MAPK/ERK pathways are involved in the pathogenesis of oral lymphatic malformations.