Abstract
Vascular endothelial growth factor (VEGF) is an angiogenic factor and could be involved in the pathogenesis of salivary gland tumors. VEGF exerts its biological function by binding to its receptors, VEGFR1 and VEGFR2. An alternative splice variant of VEGF (VEGFxxxb) is an anti-angiogenic factor. Binding VEGF165b with VEGFR2 results in an impaired angiogenic response. The imbalance of VEGFxxx and VEGFxxxb isoforms can underpin pathological angiogenesis. The purpose of this study was to evaluate and compare the expression of VEGF165b, VEGFR1, VEGFR2, and CD34 in benign and malignant parotid gland tumors and to explore the possible correlations between their expression and clinicopathological features of tumors. The study was performed on archived paraffin-embedded tissue samples derived from 70 patients with benign and malignant parotid gland tumors (25 with malignant tumors, 23 with pleomorphic adenoma and 22 with Warthin's tumor). Immunohistochemical staining of selected tissue sections was performed using monoclonal antibodies. Immunohistochemical staining of selected molecules was used for evaluation of their expression in tissue sections. There were no statistically significant differences in the expression of the selected proteins localized in the tumor and surgical margin taken from the same patient. Expression of VEGFR2 correlated with VEGF165b in mixed tumors. There was a statistically significant difference in the expression of VEGFR1 in malignant tumors between females and males, and between the expression of VEGFR1 and the score of T classification in malignant tumors. VEGF165b cannot be treated as a prognostic factor. VEGF receptors correlated with selected clinicopathological data of malignant tumors, indicating their possible role as a prognostic marker. The balance of VEGF isoforms have a limited influence on the development of parotid glands tumors. The correlation between VEGF165b and VEGFR2 in mixed tumors suggests the existence of an additional antiangiogenic pathway in poorly vascularized mixed tumors.
Highlights
Malignant salivary gland tumors are highly invasive and frequently result in distant metastasis
VEGF165b cannot be treated as a prognostic factor
Vascular endothelial growth factor (VEGF) receptors correlated with selected clinicopathological data of malignant tumors, indicating their possible role as a prognostic marker
Summary
Malignant salivary gland tumors are highly invasive and frequently result in distant metastasis. The ability of cancer cells to invade stroma and to metastasize to both the regional lymph nodes and distant tissue is a complex, multistage process. Specific angiogenic molecules produced by tumor cells stimulate the surrounding capillary endothelial cells resulting in angiogenesis into tumor tissues. The vascular endothelial growth factor (VEGF) is the most potent factor in the neovascularization of several neoplasms of salivary glands, especially adenoid cystic carcinomas (ACC) and mucoepidermoid carcinomas.[1,2,3,4,5,6] VEGF is a selective mitogen for vascular endothelial cells, which promotes angiogenesis and induces vascular permeability and its inhibition could be integrated into treatment strategies.[3] Several studies have evaluated whether
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