Neither expression of VEGF-C/D nor lymph vessel density supports lymphatic invasion as the mechanism responsible for local spread of recurrent salivary pleomorphic adenoma

Abstract

Recent research suggests that multinodular recurrent pleomorphic adenoma (PA) might result from cell migration through lymphatics. Lymphangiogenesis in malignancies is mediated by vascular endothelial growth factors C and D (VEGF-C/D). We studied the expression of VEGF-C/D in PA by immunohistochemistry as well as lymphatic vessel density (LVD). In 6 non-recurrent, 4 primary-to-recur, and 10 recurrent PAs, VEGF-C/D expression was assessed by immunohistochemistry. Staining was scored in terms of staining intensity (0 = absent to 3 = strong), and the percentage of positive tumor cells (scored as 0 (0-19 %), 1 (20-39 %), 2 (40-50 %), and 3 (60-100 %)) and a sum score were calculated. Intra- and peritumoral LVD was assessed by counting of LV after immunostaining, using the D2-40 antibody. All but one sample were VEGF-C negative. The differences in VEGF-D expression between non-recurrent, primary-to-recur, and recurrent PAs were not significant (p>0.05). VEGF-D expression did not correlate with peritumoral LVD (p>0.05). Our study revealed a significant difference between intra- and peritumoral LVD values when comparing individual and all sample groups (p=0.01). The lack of VEGF-C expression and of significant differences in VEGF-D expression and peritumoral LVD between patients with non-recurrent, primary-to-recur, and recurrent PAs does not support the lymphangiogenic local spread hypothesis

CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

“…It was generally accepted as neoplastic invasion and migration when tumour cells aggressively grew from primary lesions to surrounding tissues, blood circulation and lymphatic circulation 25. Interestingly, ncRNAs (eg circRNA, lncRNA and miRNA) have been documented to regulate cancers’ progression through modulating DNA structures, transcription of RNAs and translation of proteins 26, 27…”

Comparison of lymphatic vessel density and expression of VEGF-C and VEGF-D lymphangiogenic factors in Warthin's tumours and oncocytic adenomas

“…Information regarding the expression of the major lymphangiogenic factors in salivary gland tumours is very limited. In our two previous papers, we demonstrated moderate to strong VEGF-C and VEGF-D immunoreactivity in all cell types of salivary adenoid cystic carcinomas 27 and expression of only the latter cytokine in the cells of epithelial as well as mesenchymal component of pleomorphic adenomas 44 . Moreover, moderate expression of primarily haemangiogenic VEGF(A), known to cooperate with VEGF-C in the regulation of lymphangiogenesis 59 was reported in the epithelial and some stromal lymphoid cells of WTs by Faur et al 29 and Nakamura et al…”

“…They were numerous in the stroma of the former lesions, but very sporadic in the latter. Scarcity of these lymphatics has been reported in primary and recurrent pleomorphic adenomas, too 44,28 . In basal cell adenoma, the number of intratumorous vessels was also shown to be low, but exceeding that in pleomorphic adenoma 46 .…”

“…Analogic distribution of lymphatic network has been reported not only in WT (ref. 47 ) but also in pleomorphic adenoma 28,44 and basal cell adenoma 46 . In our cases of WT, the intratumorous lymphatics were seen solely in the lymphoid stroma.…”

“…Of these mainly pleomorphic adenomas have been analyzed. Neither primary nor recurrent lesion showed any intratumorous lymphatics 44,45 . Remarkably, Soares et al 46 demonstrated significantly higher density of the intratumorous lymphatic network in basal cell adenomas than that of pleomorphic adenoma.…”