Merkel cell carcinoma induces lymphatic microvessel formation

Background: Merkel cell carcinoma (MCC) is a rare, highly malignant neuroendocrine tumor of the skin characterized by frequent lymphatic metastasis. Objective: We sought to identify lymphovascular anatomy and expression profiles of lymphangiogenic cytokines to give an opinion on lymphangiogenesis in...

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Main Authors: Werchau, Siegfried Arthur (Author) , Toberer, Ferdinand (Author) , Enk, Alexander (Author) , Helmbold, Peter (Author)
Format: Article (Journal)
Language:English
Published: August 2012
In: Journal of the American Academy of Dermatology
Year: 2012, Volume: 67, Issue: 2, Pages: 215-225
ISSN:1097-6787
DOI:10.1016/j.jaad.2011.09.002
Online Access:Verlag, Volltext: http://dx.doi.org/10.1016/j.jaad.2011.09.002
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0190962211009601
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Author Notes:Siegfried Werchau, Ferdinand Toberer, Alexander Enk, Reinhard Dammann, and Peter Helmbold
Description
Summary:Background: Merkel cell carcinoma (MCC) is a rare, highly malignant neuroendocrine tumor of the skin characterized by frequent lymphatic metastasis. Objective: We sought to identify lymphovascular anatomy and expression profiles of lymphangiogenic cytokines to give an opinion on lymphangiogenesis in MCC. Methods: We studied lymphatic microanatomy and lymphangiogenic cytokines in 27 MCC by immunohistology or immunofluorescence (D2-40, lymphatic vessel endothelial hyaluronan receptor [LYVE-1], vascular endothelial growth factor [VEGF] receptor-3, VEGF-C, VEGF-D, Ki67/MiB-1, CD68/PG-M1, CD68/KP1, CD163), Merkel cell polyomavirus-specific polymerase chain reaction, and coanalysis with clinical and histologic data. Results: We found a more than 3-fold increase in the mean density of absolute numbers of small lymphatic capillaries (diameter <10 μm) and a more than 8-fold increase in the median ratio of the number of small to large lymphatics (<10/≥10 μm) paratumorally compared with intraindividual controls. VEGF-C+CD68+ CD163+ cells (interpreted as M2 macrophages) could be identified as an important potentially lymphangiogenesis-inducing cell type. Limitations: Partially lacking follow-up data limited the analysis of the prognostic impact. Conclusions: Our findings strongly indicate lymphangiogenesis in MCC driven by VEGF-C+CD68+ CD163+ M2 macrophages.
Item Description:Published online: September 4, 2011
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Physical Description:Online Resource
ISSN:1097-6787
DOI:10.1016/j.jaad.2011.09.002