ABSTRACT
DNA repair systems play a critical role in protecting the human genome against cumulative damage. The apurinic/apyrimidinic endonuclease 1 is a protein involved in DNA base excision repair and its expression still needs to be investigated in salivary gland tumors. The objective of this study is to analyze the immunoexpression of apurinic/apyrimidinic endonuclease 1 in pleomorphic adenomas and carcinomas ex pleomorphic adenomas of the salivary glands. A total of 33 pleomorphic adenomas and 16 carcinomas ex pleomorphic adenomas of the salivary glands underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed quantitatively. For statistical analysis, Mann-Whitney test was performed and a significance level was set at p ≤ 0.05. All analyzed tumors (n = 49) were positive for apurinic/apyrimidinic endonuclease 1. However, there was a higher median expression in carcinomas ex pleomorphic adenomas (p < 0.001). There was no difference between this protein immunoexpression and tumors of major or minor salivary gland. Overexpression was found mainly in cases of carcinomas ex pleomorphic adenomas with lymph node metastasis (p = 0.002) and invasive growth (p = 0.003), when compared to cases without metastasis and without capsular invasion (intracapsular pattern). Our findings revealed that apurinic/apyrimidinic endonuclease 1 is downregulated in pleomorphic adenomas and overexpressed in carcinomas ex pleomorphic adenomas, suggesting that this protein is possibly deregulated in pleomorphic adenoma malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior in carcinomas ex pleomorphic adenomas, which suggests that this protein may represent a prognostic biomarker in the studied salivary gland tumors.
Subject(s)
Adenoma, Pleomorphic , Carcinoma , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , Salivary Gland Neoplasms , Adenoma, Pleomorphic/genetics , Adenoma, Pleomorphic/pathology , Adult , Carcinoma/genetics , Carcinoma/pathology , Cell Transformation, Neoplastic/genetics , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Male , Middle Aged , Predictive Value of Tests , Proteomics/methods , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Salivary Glands/pathologyABSTRACT
Rho GTPases are proteins that regulate cell cycle, shape, polarization, invasion, migration, and apoptosis, which are important characteristics of normal and neoplastic cells. Rho GTPases expression has been reported in normal tooth germ and several pathologies; however, it has not been evaluated in ameloblastomas. The aim of this study was to analyze the expression and distribution of RhoA, RhoB, Rac1, and Cdc42 Rho GTPases in solid and unicystic ameloblastomas. Three-micrometer sections from paraffin-embedded specimens were evaluated by using an avidin-biotin immunohistochemical method with antibodies against the proteins mentioned above. RhoA and RhoB staining was observed in a high number of cells (P < 0.05) and greater intensity in non-polarized ones. Rac1 was not observed, and Cdc42 did not show any statistical differences between the number of non-polarized and basal positive cells (P > 0.05). Upon comparing the studied ameloblastomas, a higher number of positive cells in the unicystic variant was observed than that in the solid one (P < 0,05). The results obtained suggest that these GTPases could play a role in the ameloblastoma neoplastic epithelial cell phenotype determination (polarized or non-polarized), as well as in variant (solid or unicystic) and subtype (follicular or plexiform) determination. Furthermore, they could participate in solid ameloblastoma invasion mechanisms.
Subject(s)
Ameloblastoma/enzymology , Jaw Neoplasms/enzymology , rho GTP-Binding Proteins/metabolism , Ameloblastoma/pathology , Humans , Immunohistochemistry , Jaw Neoplasms/pathology , Tissue Distribution , cdc42 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/metabolism , rhoA GTP-Binding Protein/metabolism , rhoB GTP-Binding Protein/metabolismABSTRACT
Adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) are malignant neoplasms of salivary glands, which are similar in histologic patterns but very different in clinical behavior, treatment and prognosis. Galectin-3 is a multifunctional protein of a growing family of beta-galactoside-binding animal lectins, which is implicated in a variety of biological events such as tumor cell adhesion, proliferation, differentiation and angiogenesis. This protein was found to be implicated in cellular transformation and a correlation between its expression and cancer progression and metastasis has been described. The aim of this study was to determine the galectin-3 immunoprofile in 14 cases of ACC (2 cases of tubular subtype, 4 cases of solid subtype and 8 cases of cribriform subtype) and in 12 cases of PLGA with different histologic patterns, including lobular, tubular and cribriform aspects. Moreover, slides of normal salivary glands were included. In normal salivary glands there was strong nuclear and cytoplasmic staining for galectin-3 in ductal luminal cells. ACC showed specific staining in luminal cells mainly in the nuclei. In the tubular subtype of ACC, galectin-3 strongly stained luminal cells of the ductiform structures. The cribriform and solid subtypes showed a few positive luminal cells of small ducts present in the cribriform structures and in solid nests respectively. In the cases of PLGA, independent of the histologic architecture, all tumor cells revealed a positive cytoplasmic reaction. Galectin-3 expression seems to be related to cell differentiation more than to tumor progression and prognosis in the neoplasms studied.
