PMID- 19892405
OWN - NLM
STAT- MEDLINE
DCOM- 20100224
LR  - 20151119
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Linking)
VI  - 117
IP  - 2
DP  - 2010 Feb
TI  - Intraocular tumor-associated lymphangiogenesis a novel prognostic factor for 
      ciliary body melanomas with extraocular extension?
PG  - 334-42
LID - 10.1016/j.ophtha.2009.06.057 [doi]
AB  - PURPOSE: To evaluate whether intraocular tumor-associated lymphangiogenesis 
      contributes to prognosis of ciliary body melanomas with extraocular extension and 
      to study its association with other tumor characteristics. DESIGN: Nonrandomized, 
      retrospective case series. PARTICIPANTS: Twenty consecutive patients enucleated 
      for a malignant melanoma of the ciliary body with extraocular extension. METHODS: 
      Lymphatic vessels were identified using lymphatic vascular endothelial-specific 
      hyaluronic acid receptor-1 (LYVE-1) and podoplanin as specific 
      immunohistochemical markers for lymphatic vascular endothelium. Baseline tumor 
      characteristics included intra- and extraocular tumor size, 2009 tumor, node, 
      metastasis (TNM) classification, route of extraocular spread, tumor cell type, 
      mitotic rate, Ki-67 proliferation-index, microvascular patterns and density, 
      tumor-infiltrating lymphocytes and macrophages, and expression of human leukocyte 
      antigen (HLA) class I and insulin-like growth factor-1 receptor. Kaplan-Meier and 
      Cox regression analyses of melanoma-specific survival were performed. MAIN 
      OUTCOME MEASURES: Prevalence of intraocular LYVE-1(+)/podoplanin(+) lymphatic 
      vessels and association with intraocular tumor characteristics and 
      metastasis-free survival. RESULTS: Intraocular LYVE-1(+) and podoplanin(+) 
      lymphatic vessels could be detected in 12 (60%) of 20 ciliary body melanomas with 
      extraocular extension. Presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic 
      vessels was significantly associated with larger intra- (P = 0.002) and 
      extraocular tumor size (P<0.001), higher TNM categories (P = 0.004), epithelioid 
      cellularity (P = 0.016), higher mitotic rate (P = 0.003), higher Ki-67 
      proliferation-index (P = 0.049), microvascular networks (P = 0.005), higher 
      microvascular density (P = 0.003), more tumor-infiltrating macrophages (P = 
      0.002), higher expression of HLA class I (P = 0.046), and insulin-like growth 
      factor-1 receptor (P = 0.033), but not significantly with route of extraocular 
      spread (P = 0.803), and tumor-infiltrating lymphocytes (P = 0.069). 
      Melanoma-specific mortality rates increased significantly with the presence of 
      intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels (P = 0.008). By 
      multivariate Cox regression, tumor size (hazard ratio, 14.40; P = 0.002), and 
      presence of intraocular lymphatic vessels (hazard ratio, 8.09; P = 0.04) were 
      strong prognostic predictors of mortality. CONCLUSIONS: Intraocular peritumoral 
      lymphangiogenesis seems to be associated with an increased mortality risk in 
      patients with ciliary body melanomas and extraocular extension. This association 
      may be primarily because of an association of intraocular lymphangiogenesis with 
      greater tumor size and increased malignancy.
CI  - Copyright (c) 2010 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Heindl, Ludwig M
AU  - Heindl LM
AD  - Department of Ophthalmology and Eye Hospital, Ophthalmic Pathology Laboratory, 
      Friedrich-Alexander University Erlangen-Nurnberg, Erlangen, Germany. 
      ludwig.heindl@uk-erlangen.de
FAU - Hofmann, Tanja N
AU  - Hofmann TN
FAU - Adler, Werner
AU  - Adler W
FAU - Knorr, Harald L J
AU  - Knorr HL
FAU - Holbach, Leonard M
AU  - Holbach LM
FAU - Naumann, Gottfried O H
AU  - Naumann GO
FAU - Kruse, Friedrich E
AU  - Kruse FE
FAU - Cursiefen, Claus
AU  - Cursiefen C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091104
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (LYVE1 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (PDPN protein, human)
RN  - 0 (Vesicular Transport Proteins)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/metabolism
MH  - Ciliary Body/metabolism/*pathology
MH  - Female
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Ki-67 Antigen/metabolism
MH  - *Lymphangiogenesis
MH  - Lymphatic Metastasis
MH  - Lymphatic Vessels/metabolism/*pathology
MH  - Lymphocytes, Tumor-Infiltrating/pathology
MH  - Male
MH  - Melanoma/metabolism/mortality/*secondary
MH  - Membrane Glycoproteins/metabolism
MH  - Middle Aged
MH  - Prognosis
MH  - Receptor, IGF Type 1/metabolism
MH  - Retrospective Studies
MH  - Survival Rate
MH  - Uveal Neoplasms/metabolism/mortality/*pathology
MH  - Vesicular Transport Proteins/metabolism
EDAT- 2009/11/07 06:00
MHDA- 2010/02/25 06:00
CRDT- 2009/11/07 06:00
PHST- 2009/02/12 00:00 [received]
PHST- 2009/06/15 00:00 [revised]
PHST- 2009/06/23 00:00 [accepted]
PHST- 2009/11/07 06:00 [entrez]
PHST- 2009/11/07 06:00 [pubmed]
PHST- 2010/02/25 06:00 [medline]
AID - S0161-6420(09)00732-5 [pii]
AID - 10.1016/j.ophtha.2009.06.057 [doi]
PST - ppublish
SO  - Ophthalmology. 2010 Feb;117(2):334-42. doi: 10.1016/j.ophtha.2009.06.057. Epub 
      2009 Nov 4.