Aquaporin 1, 3, and 5 Patterns in Salivary Gland Mucoepidermoid Carcinoma: Expression in Surgical Specimens and an In Vitro Pilot Study.

Salivary gland aquaporins (AQPs) are essential for the control of saliva production and maintenance of glandular structure. However, little is known of their role in salivary gland neoplasia. Salivary gland tumors comprise a heterogeneous group of lesions, featuring variable histological characteristics and diverse clinical behaviors. Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. The aim of this study was to evaluate the expression of AQP1, AQP3, and AQP5 in 24 MEC samples by immunohistochemistry. AQP1 expression was observed in vascular endothelium throughout the tumor stroma. AQP3 was expressed in epidermoid and mucosal cells and AQP5 was expressed in mucosal cells of MEC. These proteins were expressed in the human MEC cell line UH-HMC-3A. Cellular ultrastructural aspects were analyzed by electron microscopy to certificate the tumor cell phenotype. In summary, our results show that, despite the fact that these molecules are important for salivary gland physiology, they may not play a distinct role in tumorigenesis in MEC. Additionally, the in vitro model may offer new possibilities to further investigate mechanisms of these molecules in tumor biology and their real significance in prognosis and possible target therapies.

Avaliação da expressão de aquaporinas em carcinoma mucoepidermóide da glândula salivar / Evaluation of the expression of aquaporins in mucoepidermoid carcinoma of the salivary gland

As aquaporinas (AQPs) pertencem a uma família de 13 pequenos canais de proteína transmembrana, envolvidos no transporte de água e solutos sendo fundamentais na fisiologia do organismo. Nas glândulas salivares, as aquaporinas têm sido consideradas muito relevantes para o controle da produção da saliva e manutenção da estrutura glandular, desde os processos de morfogênese do órgão. Entretanto, pouco se sabe acerca da participação dessas proteínas em processos neoplásicos dessas glândulas. Os tumores de glândulas salivares compreendem um grupo heterogêneo de lesões, apresentando diferentes características histológicas e comportamento clínico diverso. O carcinoma mucoepidermóide é o tumor maligno mais comum das glândulas salivares. Em muitos casos, os aspectos histopatológicos desse tumor se assemelham aos das glândulas salivares, e assim, indaga-se a participação das aquaporinas em suas estruturas, no sentido de se compreender a relação biológica da neoplasia com a do órgão normal. O objetivo desse trabalho foi a avaliação da expressão das aquaporinas AQP1, AQP3 e AQP5 em 24 amostras de carcinoma mucoepidermóide por imunoistoquímica. Dos 24 pacientes avaliados neste estudo, 11 eram mulheres e 13 homens. A mediana de idade dos indivíduos acometidos por esta lesão foi de 48,5 anos (variando de 8 a 81 anos) e o local mais frequentemente afetado em nossa amostra foi a glândula salivar menor, seguido pela parótida. Considerando os resultados da imunoistoquímica, a AQP1 não foi expressa no carcinoma mucoepidermóide, sendo expressa na parede dos vasos sanguíneos que permeiam o tumor. A AQP3 foi expressa nas células epidermóides e mucosas em 85,7% dos casos de carcinoma mucoepidermóide e a AQP5 foi expressa nas células mucosas em 60,0% dos casos de carcinoma mucoepidermóide. Não foi observada associação entre a expressão das proteínas e as características demográficas, clínicas, patológicas e nem associação da expressão das aquaporinas entre si. Na análise de sobrevida, foi observado que ausência de invasão vascular e ausência de recidiva estavam associadas a melhores taxas de sobrevida global. Apesar de não ser estatisticamente significativo, nossos resultados sugerem que pacientes com ausência de expressão de AQP3 e presença de expressão de AQP5 apresentam uma melhor sobrevida global. De forma geral, nosso estudo apresentou resultados inéditos sobre a expressão de aquaporinas em carcinoma mucoepidermóide. A expressão de aquaporinas parece estar associada ao processo de desenvolvimento/progressão do carcinoma mucoepidermóide, onde sugere-se que AQP1 poderia contribuir para o fornecimento de nutrientes essenciais para sustentar o crescimento do tumor, AQP3 poderia atuar no metabolismo tumoral, fornecendo energia pela captação de glicerol e conseqüentemente, divisão e proliferação celular e a AQP5 poderia estar mais envolvida no processo de diferenciação celular (AU)

The aquaporins (AQPs) belong to a family of 13 small transmembrane protein channels, involved in the transport of water and solutes being fundamental in the physiology of the organism. In the salivary glands, aquaporins have been considered very relevant for the control of saliva production and maintenance of the glandular structure, from the organ morphogenesis processes. However, little is known about the participation of these proteins in neoplastic processes of these glands. Tumors of salivary glands comprise a heterogeneous group of lesions, presenting different histological characteristics and diverse clinical behavior. Mucoepidermoid carcinoma is the most common malignant tumor of the salivary glands. In many cases, the histopathological aspects of this tumor resemble those of the salivary glands, and thus, the participation of the aquaporins in their structures is investigated, in order to understand the biological relation of the neoplasia with that of the normal organ. The aim of this work was to evaluate the expression of AQP1, AQP3 and AQP5 aquaporins in 24 mucoepidermoid carcinoma samples by immunohistochemistry. Of the 24 patients evaluated in this study, 11 were women and 13 men. The median age of the individuals affected by this lesion was 48.5 years (ranging from 8 to 81 years) and the most frequently affected site in our sample was the minor salivary gland, followed by the parotid gland. Considering the immunohistochemistry results, AQP1 was not expressed in the mucoepidermoid carcinoma, being expressed in the wall of the blood vessels that permeate the tumor. Aquaporin AQP3 was expressed in epidermoid and mucous cells in 85.7% of mucoepidermoid carcinoma cases and AQP5 was expressed in mucous cells in 60.0% of mucoepidermoid carcinoma cases. There was no association between the expression of the proteins and the demographic, clinical, pathological or association of the expression of the aquaporins with each other. Regarding survival analysis, it was observed that absence of vascular invasion and absence of relapse were associated with better overall survival rates. Although not statistically significant, our results suggest that patients with absence of AQP3 expression and presence of AQP5 expression have a better overall survival. In general, our study presented original results on the expression of aquaporins in mucoepidermoid carcinoma. The expression of aquaporins appears to be associated with the development/progression of mucoepidermoid carcinoma, where it is suggested that AQP1 might contribute to the supply of essential nutrients to support tumor growth, AQP3 might act on tumor metabolism, providing energy by uptake of glycerol and consequently, cell division and proliferation, and AQP5 might be involved in the process of cell differentiation (AU)