OBJECTIVES: To compare the density of lymphatic vessels and VEGF-C and VEGF-D expression in Warthin's tumours (WTs) and oncocytic adenomas (OCAs). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

• MeSH
• adenolymfom patologie   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfangiogeneze MeSH
• lymfatické cévy patologie   MeSH
• oxyfilní adenom patologie   MeSH
• patologická angiogeneze MeSH
• regulace genové exprese u nádorů fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor C metabolismus   MeSH
• vaskulární endoteliální růstový faktor D metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

AIMS: Some human neoplasms stimulate lymphangiogenesis through the over-production of vascular endothelial growth factors C/D (VEGF-C/D). Previously little attention has been paid to the mechanisms of lymphogenous spread of salivary adenoid cystic carcinoma (SACC). The current study investigates the presence of lymphatic network and the role of VEGF-C and VEGF-D in its formation. METHODS: The retrospective study was performed in 20 (12 females and 8 males) patients diagnosed with SACC. For the evaluation of VEGF-C/D immunoreactivity, semiquantitative histoscore was calculated as a sum of positive tumor cell score (range 0-3) and staining intensity (range 0-3). Lymphatic vessel density (LVD) was determined as the number of D2-40 positive lymphatic capillaries present at "hot spots". Moreover, the values of histoscores were calculated in surrounding normal parotid parenchyma and compared to those counted in tumors. LVD in the tumor center (iLVD), in its periphery (pLVD), and in healthy gland were identified. RESULTS: VEGF-C/D expression, iLVD and pLVD were higher in SACC than in normal gland. The VEGF-C/D score correlated neither with pLVD nor with iLVD. High iLVD values were associated with poor survival. CONCLUSIONS: The authors present the first study demonstrating the existence of lymphatic vessels in SACC.

• MeSH
• adenoidně cystický karcinom diagnóza   metabolismus   MeSH
• dospělí MeSH
• imunohistochemie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfangiogeneze imunologie   MeSH
• lymfatické cévy metabolismus   MeSH
• lymfatické metastázy MeSH
• mladý dospělý MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• slinné žlázy metabolismus   MeSH
• vaskulární endoteliální růstový faktor C metabolismus   MeSH
• vaskulární endoteliální růstový faktor D metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain normal blood pressure in states of interstitial Na(+) and Cl(-) accumulation. Failure of this physiological extrarenal regulatory mechanism leads to a salt-sensitive blood pressure response.

• MeSH
• chlorid sodný farmakologie   MeSH
• deoxykortikosteron farmakologie   MeSH
• dichlormethylendifosfonát farmakologie   MeSH
• exprese genu fyziologie   MeSH
• fagocyty cytologie   fyziologie   MeSH
• financování organizované MeSH
• hypertenze metabolismus   patofyziologie   MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl farmakokinetika   MeSH
• kůže metabolismus   MeSH
• lymfangiogeneze fyziologie   MeSH
• lymfatické cévy cytologie   fyziologie   MeSH
• mineralokortikoidy farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• proteinurie metabolismus   patofyziologie   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• TNF-alfa genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vaskulární endoteliální růstový faktor C genetika   metabolismus   MeSH
• vodní a elektrolytová rovnováha fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

Vascular endothelial growth factors (VEGFs) have a leading role among variety of angiogenic factors. Together with their receptors, they play an important role in endothelial cell proliferation and/or elongation, migration and vascular morphogenesis. In order to determine their possible role in malignant melanoma progression, VEGF (representing VEGFA), VEGF-C and VEGFR-1, -2, -3 immunohistochemical expression on formalin-fixed, paraffin-embedded tissue sections were evaluated. A total of 196 tissue samples consisting of 130 malignant melanomas (MM) with various vertical depth of invasion, 15 metastatic melanomas, and 66 nevi including dysplastic nevi and melanocytic nevi were analysed. Production of both VEGFs were common in benign melanocytic tumors while MM exhibited significant upregulation of VEGF (p<0.0027) and VEGF-C (p<0.0001). The proteins were also detected within stromal cells surrounding tumors, particularly in fibrocytes/ fibroblasts, macrophages and endothelial cells. They also exhibited significant increase in malignant lesions (p<0.0001). VEGFRs were localized in tumor, as well in stromal cells. Although expression of VEGF receptors was significantly higher in MM versus nevi (p<0.002 for VEGFR-1, p<0.004 for VEGFR-2 and p<0.0001 for VEGFR-3), a considerable percentage of MM were negative. There were no correlations between sentinel node positivity and all investigated proteins. When clinical outcome was evaluated, progression of the disease positively correlated with VEGF (p<0,007) and VEGF-C (p<0,008) expression VEGF (p<0.001) and VEGF-C (p<0.0001) positively correlated with nestin expression in the capillary endothelium, which was used for angiogenesis detection. Our work demonstrated that upregulation of VEGFs is associated with progression of malignant melanomas. The protein expression in the tumor microenvironment highlights their importance in malignant stromal phenotype which may serve as a potential target for the anticancer therapy.

• MeSH
• cévní endotel metabolismus   MeSH
• financování organizované MeSH
• lidé MeSH
• melanom metabolismus   patologie   MeSH
• nádory kůže metabolismus   patologie   MeSH
• prognóza MeSH
• proteiny intermediálních filament metabolismus   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptor 3 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptory vaskulárního endoteliálního růstového faktoru metabolismus   MeSH
• vaskulární endoteliální růstové faktory metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• vaskulární endoteliální růstový faktor C metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH