epidermal-growth-factor and Adenoma--Pleomorphic

During tumor development, benign neoplastic cells are influenced by the expression of cytokines, growth factors, and proteases present in the tumor microenvironment. Epidermal growth factor (EGF) is the most studied growth factor and is considered important for cell proliferation and migration. Metalloproteinases (MMPs) are also involved in tumor progression. The present study aimed to analyze the proliferation, viability and migration index of pleomorphic adenoma myoepithelial cells, in addition to the secretion of MMPs with EGF supplementation. Benign myoepithelial cells were cultured with two different EGF doses (5 and 10 ng/ml), and the influence of EGF on cell proliferation and viability, using trypan blue and MTT assays, respectively, after 24, 48, and 72 h, was evaluated. To analyze cellular morphology, hematoxylin-eosin staining and indirect immunofluorescence using the anti-vimentin antibody, was performed. In vitro migration assays were performed in Transwell chambers with an 8-μm pore covered with Matrigel and supplemented with 5 or 10 ng/ml of EGF, after 96 h. After 4 days of cell culture, ELISA was performed to determine the MMP-2 and MMP-13 levels. One-way analysis of variance (ANOVA) with post hoc Tukey test was applied, with a significance level of 0.05. The results revealed that EGF influences myoepithelial cell morphology, without alteration of proliferation and viability. The migration assay showed that EGF increased the mean index from 16 % in the control group to 40 and 76 % for 5 and 10 ng/ml of EGF, respectively. ELISA revealed that when the cells were supplemented with either of the EGF doses, an increase in MMP-2 levels was observed when compared with the control group (C). This study concludes that EGF aids in the production of MMP-2, which favors the dissolution of the basement membrane, contributing to cell migration and tumor progression, hence permitting contact between the myoepithelial cells and stroma.

Topics: Adenoma, Pleomorphic; Cell Movement; Cell Proliferation; Cell Shape; Epidermal Growth Factor; Epithelial Cells; Humans; Matrix Metalloproteinase 13; Matrix Metalloproteinase 2; Myoepithelioma; Salivary Gland Neoplasms; Signal Transduction; Tumor Cells, Cultured

To analyze the expression of ErbB-1 (Her-1 or EGFR), ErbB-2 (Her-2 or neu), ErbB-3 (Her-3) and ErbB-4 (Her-4) and their correlation in 3 different types of salivary gland tumors.. Immunohistochemical expression of epidermal growth factor (EGF), EGFR, ErbB-2, fatty acid synthase (FAS) and Ki-67 were analyzed in 41 pleomorphic adenoma (PA), in 30 mucoepidermoid carcinoma (MEC) and in 30 adenoid cystic carcinoma (ACC) and correlated with their histologic patterns.. EGF was more common in MEC and PA, but MEC had a higher percentage of strongly positive cases. EGFRc and EGFRm were both more frequent in MEC and ACC. Higher scores of ErbB-2c were observed in PA, followed by MEC and ACC. In contrast, higher scores of ErbB-2m were more common in MEC as compared to ACC and PA. FAS was most commonly found in PA and MEC. Moreover, MEC showed the highest percentage of strongly positive cases. Ki-67 was higher in MEC and ACC than in PA. From a correlation of immunomarkers with the histologic patterns, it was observed that cribriform ACC presented more expression of EGFR and high grade MEC showed a higher percentage of ErbB-2, FAS and Ki-67.. EGF, EGFR, ErbB-2 and FAS were commonly found and seem to be important in the tumorigenesis of salivary gland tumors, particularly in percentage of strongly positive cases. Ki-67 was higher in MEC and ACC than in PA. From a correlation of immunomarkers with the histologic patterns, it was observed that cribriform ACC presented more expression of EGFR and high grade MEC showed a higher percentage of ErbB-2, FAS and Ki-67.. EGF, EGFR, ErbB-2 and FAS were commonly found and seem to be important in the tumorigenesis of salivary gland tumors, particularly in MEC. (Anal Quant Cytol Histol 2009;31:280-287)

Topics: Adenoma, Pleomorphic; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Epidermal Growth Factor; ErbB Receptors; fas Receptor; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Male; Middle Aged; Receptor, ErbB-2; Salivary Gland Neoplasms

The phenotypic expression of the human epidermal growth factor (EGF) was investigated immunohistochemically in human foetal submandibular glands from the 5th to 10th month of gestation, adult normal submandibular glands and 48 cases of pleomorphic adenomas. In foetal submandibular glands, both the terminal buds and primary ducts at the intermediate stage of gestation were positive for EGF, and in particular, the outer layer cells of primary ducts showed strong EGF-immunoreactivity. EGF-positive cells decreased as the gestational stage advanced and only ductal cells were weakly positive for EGF at the terminal stage of gestation. In the adult normal submandibular gland, weak immunoreactivity for EGF was restricted to ductal cells. However, 41 (86%) of the 48 pleomorphic adenomas had EGF-positive cells which were distributed among the ductal, chondroid and myxoid portion. No EGF-immunoreactivity was detected in the solid portion of pleomorphic adenomas. These results suggest that EGF may play an important role in the growth and differentiation of foetal cells as well as the proliferation of tumour cells in pleomorphic adenomas.

Topics: Adenoma, Pleomorphic; Antibodies; Epidermal Growth Factor; Fetus; Humans; Immunohistochemistry; Phenotype; Salivary Gland Neoplasms; Submandibular Gland Neoplasms

Immunohistochemical identification of human epidermal growth factor (hEGF) was carried out in a total of 152 cases of salivary gland tumours, consisting 107 pleomorphic adenomas and their variants, 13 adenolymphomas and 32 adenoid cystic carcinomas. A high percentage of pleomorphic adenomas revealed markedly positive hEGF staining of the luminal surface cells of tubuloductal structures and of modified or neoplastic myoepithelial cells. Clear cells of the tumour showed various reactivities from very slight to strong. Eosinophilic epithelial cells of adenolymphoma gave a positive reaction for hEGF in all the cases, whereas most adenoid cystic adenoma lacked hEGF staining; however some cases showed positive staining of the tumour cells. The immunohistochemical detection of hEGF in most salivary gland tumours suggests this factor to be a possible new marker of salivary glands tumours, and to have a biological role in tumour proliferation.

Topics: Adenolymphoma; Adenoma, Pleomorphic; Carcinoma, Adenoid Cystic; Epidermal Growth Factor; Histocytochemistry; Humans; Salivary Gland Neoplasms

Immunohistochemical distribution of human epidermal growth factor (hEGF) was described in 17 cases of mixed tumour of the skin with monoclonal antibody. In normal sweat glands, epithelial cells in the secretory portion and in the transitional area between secretory portion and duct showed prominent staining for hEGF. In the salivary pleomorphic adenoma type of mixed tumour of the skin, luminal tumour cells of tubular and duct-like structures gave a very characteristic hEGF staining reaction. The tumour cells showing strong staining for hEGF were scattered throughout the solid foci in this type of mixed tumour. Tubular epithelial cells in the clear cell adenoma type also displayed a positive hEGF reaction. And apocrine mixed tumours strong staining for hEGF occurred on the apical side of tubular and ductal tumour cells. In view of the immunohistochemical staining patterns for hEGF, the histologic origin of mixed tumours of the skin is suggested to be cells in the secretory portion and those in the transitional portion between secretory portion and duct of the sweat gland.

Topics: Adenoma, Pleomorphic; Antibodies, Monoclonal; Epidermal Growth Factor; Humans; Immunohistochemistry; In Vitro Techniques; Neoplasms, Germ Cell and Embryonal; Salivary Gland Neoplasms; Sweat Gland Neoplasms