title: Analysis of caveolin-1 and phosphoinositol-3 kinase expression in primary uveal melanomas.
abstract: BACKGROUND
  To evaluate the regulation of blood supply in primary uveal melanomas through caveolin-1 (Cav-1)/phosphoinositol-3 kinase (PI3K).
  
  
  METHODS
  The expression of Cav-1 and PI3K was analysed in 51 paraffin sections of metastatic (n = 30) and non-metastastic uveal melanomas (n = 21). Two trained observers quantified Cav-1 and PI3K immunofluorescensce expression by determining intensity of staining and percentage of positive cells. The expression was correlated with known prognostic factors. Besides angiogenesis by means of endoglin expression, the normal vasculature (von Willebrand Factor expression) was evaluated semi-quantitatively. Vasculogenic mimicry (VM) was analysed by CD31/PAS staining.
  
  
  RESULTS
  All examined specimens expressed Cav-1 with a mean of 90.34% Cav-1 positive cells (range, 3.23-100%). Metastatic disease was associated with a higher Cav-1 expression. The correlation of Cav-1 with well-established prognostic factors showed a significant association between Cav-1 expression and largest tumour diameter (P = 0.022), tumour node metastasis classification (P = 0.008) and invasion of optic nerve head (P = 0.048). PI3K was expressed by all uveal melanomas with a mean of 87.28% cells showing PI3K expression. A higher level of PI3K was significantly associated with larger height (P = 0.042) and progressed tumour node metastasis stage (P = 0.016). The percentage of PI3K and Cav-1 positive cells were significantly associated (P = 0.034). For PI3K and Cav-1 expression a non-significant association with VM was shown (P = 0.064 and P = 0.072, respectively). No correlation of PI3K or Cav-1 with angiogenesis or mature vasculature was seen (P > 0.05).
  
  
  CONCLUSIONS
  Cav-1 expression may be especially up-regulated in larger uveal melanomas. As it was correlated with PI3K expression and VM in this series of uveal melanoma, Cav-1 might induce the formation of VM via the PI3K-signalling cascade.
authors.affiliation: Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Stenzel
authors.affiliation: Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
authors.forename: Aysegül
authors.initials: A
authors.lastname: Tura
authors.affiliation: Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
authors.forename: Khaled
authors.initials: K
authors.lastname: Nassar
authors.affiliation: University Eye Hospital, Centre of Ophthalmology, Eberhard-Karls University of Tuebingen,, Tuebingen, Germany.
authors.forename: Jens Martin
authors.initials: JM
authors.lastname: Rohrbach
authors.affiliation: Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.affiliation: Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lüke
authors.affiliation: Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Lüke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D053492:Elafin / Q000378:metabolism*; D000071063:Endoglin / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000201:enzymology*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D015854:Up-Regulation; D014604:Uveal Neoplasms / Q000098:blood supply / Q000201:enzymology*; D014841:von Willebrand Factor / Q000378:metabolism; D000098943:Uveal Melanoma
chemical_list: D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; D051242:Caveolin 1; C064206:ENG protein, human; D053492:Elafin; D000071063:Endoglin; C506806:PI3 protein, human; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D014841:von Willebrand Factor
keywords: angiogenesis; caveolin-1; metastasis; phosphoinositol-3 kinase; prognosis; uveal melanoma; vasculogenic mimicry