Neurofibromin expression by normal salivary glands

INTRODUCTION: Neurofibromin, a protein encoded by the NF1 gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated. AIM: To investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1. MATERIAL AND METHOD: Ten samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method. RESULTS: Neurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34). CONCLUSION: Neurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.