E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST contribute to epithelial-mesenchymal transition in salivary gland tumors.

BACKGROUND: Transcription factors are important in the epithelial-mesenchymal transition process and are possibly related to the development of a more invasive tumor phenotype. Thus, the objective of this study was to analyze the expression and identify the localization of cellular markers related to the epithelial-mesenchymal transition process in salivary gland tumors. STUDY DESIGN: The expression and localization of E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST were evaluated, using immunohistochemistry, in 48 salivary gland tumors, being 17 pleomorphic adenomas (PA), 14 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). these proteins were compared to clinical and histopathologic parameters. normal gland tissues were included for immunohistochemical comparisons. RESULTS: ACC and MEC cases showed higher expression of SNAIL compared to PA. MEC showed high expression of SLUG and TWIST. Low expression of N-CADHERIN, SNAIL, and TWIST in ACC was frequent in T3 and T4. High expression of TWIST in MEC was more frequent at age ≥ 40 years A positive correlation was only observed between N-cadherin/SNAIL in ACC, between SNAIL/TWIST in MEC, and between SLUG/TWIST in PA. CONCLUSION: This study provided insight into EMT-related proteins (E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST) and their contribution to the maintenance of morphogenesis and the development of the salivary gland tumors and showed a positive correlation among N-CADHERIN/SNAIL in ACC and SNAIL/TWIST in MEC.

Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

MicroRNAs expression pattern related to mast cell activation and angiogenesis in paraffin-embedded salivary gland tumors.

The aim of this study was evaluate the expression profile of microRNAs related to mast cells activation and angiogenesis in salivary glands tumors. METHOD: We have analyzed the expression of miR-9, miR-16, miR-17, miR-132, miR-195 and miR-221 by real-time RT-PCR, in 11 adenoid cystic carcinomas, 9 mucoepidermoid carcinomas and 11 pleomorphic adenomas. Immunohistochemical investigation was performed to detect mast cells tryptase and CD-34 for microvessels biomarkers. miR-16, miR-17, miR-132, miR-195 and miR-221 showed a decreased expression, whereas miR-9 showed an increased expression in most cases compared to normal tissues. However, in all tumors studied only miR-9 showed a statistical significant negative correlation with microvessel density (p=0.001). It was observed a higher density of mast cells in mucoepidermoid carcinomas (10.55 cells/mm2) when compared to adenoid cystic carcinomas (6.27 cells/mm2) and between mucoepidermoid carcinomas and pleomorphic adenomas (5.97células/mm2). miR-17, miR-132, miR-195 and miR-221 seem to play an important role as tumor suppressor in salivary gland tumors. In addition, the significant correlation between mast cell and microvessel density contributes to the growth and pathogenesis of these tumors and they may become strong therapeutic targets in the future.