Abstract
To compare the density of lymphatic vessels and VEGF-C and VEGF-D expression in Warthin's tumours (WTs) and oncocytic adenomas (OCAs). Twenty three WTs and 13 OCAs of the parotid gland were analyzed. Lymphatic vessels were detected using the D2-40 antibody. For evaluation of the intratumour and peritumour lymphatic vessel density (iLVD and pLVD, respectively) the area of greatest vascularisation (hot spots) was chosen, using a ×40 field, and the number of vessels per square millimeter was counted in a ×200 field. The staining intensity for VEGF-C and VEGF-D immunoreaction in the tumour cells was graded from 0 to 3. The mean iLVD and pLVD values in WTs was 4.7 (range 1-8) and 6.9 (range 3-10), those in the OCAs 1.0 (range 0-3) and 5.8 (range 2-8), respectively. The differences in the iLVD, but not pLVD between the two tumour groups were statistically significant. In both entities, the pLVD markedly outnumbered the iLVD. The intratumour vessels in the WTs were present exclusively in the lymphoid stroma. In the group of 23 WTs, 13 (56.6%), 17 (73.9%) and 10 (43.4%) samples revealed positive VEGF-C, VEGF-D and both immunoreactions, respectively. 10 of 13 (77%) cases revealed VEGF-D immunoreaction and in none of them was the VEGF-C reaction present. The tumours had a comparable high density of peritumorous lymphatic network. However, WTs markedly differed from OCAs in the number of the intratumorous vessels. These were abundant solely in the stroma of WT, while practically lacking in the neoplastic epithelium of the WT and relatively rare in OCAs. We suggest that homeostasis in both entities is mediated mainly by peritumorous lymphatics. The lymphatic drainage in WTs is also fostered exclusively by stromal lymphatics, whereas in stroma poor OCAs by the vessels present in their neoplastic epithelium. We also believe that WTs stimulate proliferation of pre-existing lymphatic capillaries by means of the paracrine secretion of VEGF-C and VEGF-D in the neoplastic as well as reactive stromal cells, while in the OCAs only the latter factor takes part in their lymphangiogenesis.
Highlights
Lymphatic vessels play an important role in tissue homeostasis, inflammations, regeneration and wound healing
Lymphatic vessel density In Warthin’s tumours (WTs), lymphatic capillaries were demonstrated in the capsule (Fig. 1) and the lymphoid (Fig. 2) but not in the epithelial component
There was a D2-40 positive reaction in basal epithelial cells and in follicular dendritic cells of the germinal centers in these entities (Fig. 2). Both peri- and intratumorous lymphatics were seen in oncocytomas, the sparse myoepithelial cells of which stained with the D2-40 antibody (Fig. 3)
Summary
Lymphatic vessels play an important role in tissue homeostasis, inflammations, regeneration and wound healing. They serve as conduits by which tumour cells colonize regional lymph nodes and invade the blood circulation. Growth and function of lymphatic vasculature are promoted by many cytokines among which vascular endothelial factor C (VEGF-C) and D (VEGF-D) are crucial[1]. These two ligands activate tyrosine kinase vascular endothelial growth factor receptor-3 (VEGFR-3) of lymphatic endothelial cells[2]. It has been demonstrated, that in some carcinomas, including those originating in the head and neck region, forced VEGF-C and -D expression and density of associated newly formed lymphatic network are significant predictors of nodal involvement and prognosis[6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]
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Schedule a callMore From: Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
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