title: Intraocular lymphatics in ciliary body melanomas with extraocular extension: functional for lymphatic spread?
abstract: OBJECTIVE
  To assess the functional significance of intraocular tumor-associated lymphatic vessels in ciliary body melanomas with extraocular extension.
  
  
  METHODS
  Twelve consecutive patients enucleated for a malignant melanoma of the ciliary body with extraocular extension and immunohistochemical presence of intraocular LYVE-1-positive and podoplanin-positive lymphatic vessels were examined for proliferation status and tumor invasion into tumor-associated lymphatics. Proliferating lymphatic vessels were identified using LYVE-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as the proliferation marker. Tumor invasion into lymphatic vessels was assessed using Melan-A as the melanoma marker. Kaplan-Meier analyses of survival and metastasis were performed.
  
  
  RESULTS
  Intraocular proliferating lymphatic vessels were detected in all 12 ciliary body melanomas with extraocular extension. The ratio of proliferating lymphatics was significantly higher in the intraocular vs extraocular tumor compartment (P < .001). Extraocular lymphatic invasion by tumor cells was observed in 5 patients (42%), intraocular lymphatic invasion in 4 (33%), and synchronous intraocular and extraocular lymphatic invasion in 3 (25%). Detection of melanoma cells in intraocular and extraocular lymphatic vessels was significantly associated with higher risks of lymphatic spread (P < .001) and lower metastasis-free survival rates (P = .03).
  
  
  CONCLUSIONS
  Intraocular tumor-associated lymphatic vessels contain proliferating endothelial cells and can be invaded by cancer cells in ciliary body melanomas with extraocular extension. Lymphatic invasion by tumor cells seems to be associated with an increased risk of lymphatic spread and mortality in these affected patients.
authors.affiliation: Department of Ophthalmology and Eye Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Germany. ludwig.heindl@uk-erlangen.de
authors.forename: Ludwig M
authors.initials: LM
authors.lastname: Heindl
authors.forename: Tanja N
authors.initials: TN
authors.lastname: Hofmann
authors.forename: Falk
authors.initials: F
authors.lastname: Schrödl
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Holbach
authors.forename: Friedrich E
authors.initials: FE
authors.lastname: Kruse
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002924:Ciliary Body / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D014604:Uveal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D058965:MART-1 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D033921:Vesicular Transport Proteins; C119248:LYVE1 protein, human; C548667:MLANA protein, human; C117468:PDPN protein, human; D000098853:Podoplanin