Expression of vascular endothelial growth factor-A, matrix metalloproteinase-9, and extravascular matrix patterns and their correlations with clinicopathologic parameters in posterior uveal melanomas

Jpn J Ophthalmol. Sep-Oct 2007;51(5):325-331. doi: 10.1007/s10384-007-0456-z. Epub 2007 Oct 5.


Purpose: To assess extravascular matrix patterns (EMP) and expression of vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) in posterior uveal melanomas and their correlations with histopathologic parameters and metastasis.

Methods: This study was conducted on 100 consecutive eyes enucleated for posterior uveal melanomas. All tumors were examined by immunohistochemical techniques for VEGF-A and MMP-9 expression, and the presence of EMPs was assessed on routine paraffin sections stained with reticulin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration, and scleral and optic nerve invasion were analyzed by using light microscopy. No eyes had received prior treatment such as radiotherapy or transpupillary thermotherapy.

Results: Identified histopathologically, cell types were spindle cells in 60% of the cases, mixed cells in 14%, and epithelioid cells in 26% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 84% and 72% of the tumors, respectively. Microvascular loops and/or networks were seen in 34% of the tumors, with the remaining 16% of the tumors displaying an arc pattern, 21% displaying a parallel pattern, and 29% displaying the normal pattern. The relationships between VEGF-A and MMP-9 expression and necrosis, the degree of lymphocyte infiltration, mitotic rate, and the formation of loop and network patterns were found to be statistically significant (P < 0.05). Metastatic disease developed in 14 patients during follow up.

Conclusions: The incidence of metastatic melanoma increased with the increasing expression of VEGF-A and MMP-9. Our data suggest that increasing VEGF-A and MMP-9 expression and the EMP can be used as independent prognostic factors in the management of posterior uveal melanoma following enucleation.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Middle Aged
  • Prognosis
  • Severity of Illness Index
  • Uveal Neoplasms / metabolism*
  • Uveal Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / biosynthesis*


  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9