Immunohistochemical Evaluation of Epidermal Growth Factor Receptor (EGFR), MMP-2 and Heparanase in Pleomorphic Adenoma of Salivary Glands

Abstract

Background: Salivary gland tumors are morphologically and clinically diverse group of neoplasms .The most common benign tumor is the pleomorphic adenoma, it contains the epithelial, myoepithelial and mesenchymal component, with variable morphological patterns. Epidermal growth factor receptor (EGFR) is a 170 KD glycoprotein which has a tyrosine kinase activity. It is found at abnormally high levels on the surface of many types of cells, so these cells may divide excessively in the presence of epidermal growth factor.MMP-2 is a widely studied matrix metalloproteinase which participates in extracellular matrix (ECM) degradation, having a wide range of substrates and able to degrade type I, IV, V, VII and X collagens, laminin, elastin, fibronectin and proteoglycans. Heparanase (HPA) is an endo-β-D-glucuronidase that has the activity of cleaving heparan sulfate (HS) side chains of heparan sulfate proteoglycans (HSPGs), the major proteoglycans of the extracellular matrix (ECM) and basement membrane (BM) which play a key role in preventing tumor cells invasion and metastasis. Aims of the study: This study aimed to evaluate the expression of EGFR, MMP-2 and heparanase in pleomorphic adenoma of salivary glands and to correlate the expression of the aforementioned biomarkers with the clinical parameters, histological subtypes and components, and with each other as well. Materials and methods: Twenty five paraffin blocks of pleomorphic adenoma were included in this study. Sections immunohistochemically stained with anti EGFR, anti MMP-2 and anti heparanase monoclonal antibodies (Mabs). Results: Positive EGFR, MMP-2 and hepranase immunohistochemical expression was found in 22 (88%), 14(56%) and 21 (84%) of the studied cases respectively. Statistically non- significant correlation was found among the aforementioned markers with each other, and between the markers and any of the clinical parameters and histological classifications, except a statistically highly significant negative correlation revealed regarding EGFR expression with the squamous cells of epithelial component (p =0.001) and a highly significant positive correlation found regarding MMP-2 expression with the chondroid stromal component (0.003). Conclusions: Histological variation of pleomorphic adenoma has no influence on its biological behavior concerning EGFR, MMP-2 and heparanase expression. The immunoscores reorded in this study are expected to contribute to a better understanding of the biological behavior of PA.