Salivary levels and immunohistochemical expression of selected angiogenic factors in benign and malignant parotid gland tumours

Katarzyna Błochowiak,Magdalena Bodnar,Jerzy Sokalski,Ewelina Golusińska,Andrzej Marszałek,Dorota Trzybulska,Henryk Witmanowski

doi:10.1007/s00784-018-2524-9

Abstract

ObjectivesAngiogenesis underlies tumour growth and metastasis through hepatocyte growth factor (HGF), epithelial growth factor (EGF), and vascular endothelial growth factor (VEGF). The aim of this study was to determine the levels of VEGF, EGF, HGF, HGFR (hepatocyte growth factor receptor), and SRSF1 (serine-rich protein splicing factor-1) in patients with parotid gland tumours and in healthy controls via ELISA in parotid saliva. Immunohistochemical expression of anti-angiogenic isoform of VEGF165b subunit, VEGFR1, VEGFR2, and microvessel density (CD34) were assessed in the tumour tissue and in the non-tumorous surrounding margins.Materials and methodsThe study included 48 patients with benign and malignant parotid gland tumours and 15 healthy controls.ResultsComparison of VEGF, EGF, and HGF in tumour and non-tumorous tissues showed no significant differences and no correlations with tumour stage. The salivary VEGF concentration was significantly higher in patients with pleomorphic adenoma and Warthin’s tumour. No significant correlation was found between expression of VEGF165b and VEGFR2 in tumours and non-tumor surgical margins.ConclusionsThe increased salivary VEGF reflects changes in affected parotid glands, but it cannot be used as a prognostic and differentiative factor for parotid tumours.Clinical relevanceReciprocal relations between growth factors suggest an overlapping pathway of secretion and activity.

Highlights

Tumours of the salivary glands are uncommon, accounting for 3–6% of all head and neck tumours [1, 2]
vascular endothelial growth factor (VEGF) has been implicated in intratumoral microvessel density (MVD) and metastatic spread, and for these reasons, it is considered a prognostic factor for many cancers, including salivary gland tumours and oral squamous cell carcinomas [1, 8]
Salivary concentration of VEGF does correlate with the levels of other growth factors; as a result, for comprehensive assessment of angiogenesis, the levels of these other growth factors should be determined

Summary

Introduction

Tumours of the salivary glands are uncommon, accounting for 3–6% of all head and neck tumours [1, 2]. Several growth factors—including hepatocyte growth factor (HGF), epithelial growth factor (EGF), and vascular endothelial growth factor (VEGF)—are known to be involved in the pathogenesis of salivary gland tumours [5]. In both normal and neoplastic cells, HGF provides a strong mitogenic influence on cell motility; it is a powerful angiogenetic factor and exerts powerful anti-apoptotic activity. Two families of VEGF proteins are formed by an alternative splice-acceptor-site, which gives two sequences differing in their angiogenic properties [10,11,12,13] These two isoforms bind to VEGFR2 with the same affinity, but the binding of VEGF165b results in an insufficient tyrosine phosphorylation/activation of VEGFR2 and incomplete or transient downstream signaling. Serine-rich protein splicing factor 1 (SRSF1) can change the proportion of VEGF165 and VEGF165b and regulate alternative splicing [10]

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