title: [Expression of EphA2 in Metastatic and Non-Metastatic Primary Uveal Melanoma].
abstract: BACKGROUND
  Little is known about how the expression of Ephrin type-A receptor 2 (EphA2) influences cell-cell adhesion, migration, angiogenesis, and the formation of vasculogenic mimicry (VM) channels in uveal melanomas or how this may be related to the rate of metastasis.
  
  
  METHODS
  Paraffin embedded sections of 50 histopathologically well characterised primary uveal melanomas (mean largest tumour diameter: 16.3 mm) were evaluated with respect to the expression of EphA2. Systemic metastasis was detected in 29 patients. The remaining 21 patients were followed for a mean of 10 years. Tumour angiogensis was analysed by endoglin expression (CD105), the activity of the mature vascular system (von Willebrand factor) and the presence of VM (CD31/PAS staining).
  
  
  RESULTS
  All uveal melanomas expressed EphA2, with a mean of 95.93 % positive cells ± SD: 6.3 %. There was no significant association between EphA2 and the rate of metastases (p = 0.196), endoglin expression (p = 0.652), VM (p = 0.267) or with any other clinical or histopathological factors (p < 0.05). However, there was significant up-regulation of EphA2 in the nucleus of the metastatic uveal melanoma subgroup, while cytoplasmatic localisation in the subgroup was associated with better prognosis (p = 0.006). There were low levels of EphA2 expression in the specific retinal layers, the ciliary and corneal epithelium, and the choroidal and corneal endothelium.
  
  
  CONCLUSIONS
  Nuclear expression of EphA2 in this series of large tumours was significantly associated with an increased rate of metastasis. On the other hand, cytoplasmic localisation was associated with a better prognosis. As there was no correlation between EphA2 expression and angiogenesis, the mature vasculature or VM, EphA2 appears to become less important in the advanced stages of the disease.
authors: Klinik für Augenheilkunde, Universität zu Lübeck.
authors: V
authors: V
authors: Vukoja
authors: Klinik für Augenheilkunde, Universität zu Lübeck.
authors: T
authors: T
authors: Brandenbusch
authors: Klinik für Augenheilkunde, Universität zu Lübeck.
authors: A
authors: A
authors: Tura
authors: Klinik für Augenheilkunde, Universität zu Lübeck.
authors: K
authors: K
authors: Nassar
authors: Department für Augenheilkunde, Forschungsbereich Geschichte der Augenheilkunde/Ophthalmopathologisches Labor, Eberhard-Karls-Universität Tübingen.
authors: D J M
authors: DJ
authors: Rohrbach
authors: Klinik für Augenheilkunde, Universität zu Lübeck.
authors: M
authors: M
authors: Lüke
authors: Klinik für Augenheilkunde, Universität zu Lübeck.
authors: S
authors: S
authors: Grisanti
authors: Klinik für Augenheilkunde, Universität zu Lübeck.
authors: J
authors: J
authors: Lüke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D036104:Receptor, EphA2 / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014604:Uveal Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
chemical_list: D014408:Biomarkers, Tumor; D036104:Receptor, EphA2