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Verfasst von:Toberer, Ferdinand [VerfasserIn]   i
 Hänßle, Holger [VerfasserIn]   i
 Heinzel‐Gutenbrunner, M. [VerfasserIn]   i
 Enk, A. [VerfasserIn]   i
 Hartschuh, Wolfgang [VerfasserIn]   i
 Helmbold, Peter [VerfasserIn]   i
 Kutzner, H. [VerfasserIn]   i
Titel:Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma
Titelzusatz:expression of hypoxia-inducible factor-1α and its central downstream factors
Verf.angabe:F. Toberer, H.A. Haenssle, M. Heinzel‐Gutenbrunner, A. Enk, W. Hartschuh, P. Helmbold, H. Kutzner
Jahr:2021
Jahr des Originals:2020
Umfang:7 S.
Fussnoten:First published: 12 May 2020 ; Gesehen am 23.02.2021
Titel Quelle:Enthalten in: European Academy of Dermatology and VenereologyJournal of the European Academy of Dermatology and Venereology
Ort Quelle:Oxford [u.a.] : Wiley-Blackwell, 1991
Jahr Quelle:2021
Band/Heft Quelle:35(2021), 1, Seite 88-94
ISSN Quelle:1468-3083
Abstract:Background Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. Objectives To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. Methods The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). Results HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV− tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV− tumours (QS: 5.40 ± 3.43, P = 0.019). Conclusions Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV− tumours seem to show relevant differences.
DOI:doi:10.1111/jdv.16600
URL:kostenfrei: Volltext ; Verlag: https://doi.org/https://doi.org/10.1111/jdv.16600
 kostenfrei: Volltext: https://www.onlinelibrary.wiley.com/doi/abs/10.1111/jdv.16600
 DOI: https://doi.org/10.1111/jdv.16600
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1749167026
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