title: Merkel cell carcinoma induces lymphatic microvessel formation.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Dermatology, University of Heidelberg, Heidelberg, Germany.
authors: Siegfried
authors: S
authors: Werchau
authors: Ferdinand
authors: F
authors: Toberer
authors: Alexander
authors: A
authors: Enk
authors: Reinhard
authors: R
authors: Dammann
authors: Peter
authors: P
authors: Helmbold
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019394:Ki-67 Antigen; D011956:Receptors, Cell Surface; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3; D033921:Vesicular Transport Proteins; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C119248:LYVE1 protein, human