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S. Di Cesare, S. Callejo, M. Greenberg, J. Isenberg, E. Antecka, M. N. Burnier, Jr.; Elevated PAI-1 Expression in Primary Uveal Melanoma and Patient Plasma Correlate With Prognosis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):859.
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Plasminogen activator inhibitor-1 (PAI-1) is a 45 kDa serine protease that acts mainly as a fribrinolytic inhibitor. It has been previously associated with tumor growth, angiogenesis, and neoplastic progression. We aimed to study the prognostic significance of PAI-1 in uveal melanoma (UM).
A total of 43 formalin-fixed paraffin-embedded (FFPE) primary UM were used. Each block was sectioned to a thickness of 10µm. The High Pure RNA Paraffin Kit (Roche) was used to extract total RNA from each of the 10µm sections. The quantity and quality of the total RNA extracted from each specimen was evaluated using a NanoDrop (ND-3300), qPCR, and an Agilent RNA 6000 Bioanalyzer. All validated RNA samples were then processed and analyzed using the DASL method (Illumina). All samples were run in duplicate. Gene expression values generated from the array were analyzed using the Genespring GX software (Agilent). A commercially available ELISA kit (R&D) was used to verify protein levels of PAI-1 in plasma samples from 11 UM patients. All patient samples were run in duplicate and normalized to a PAI-1 protein standard curve (ng/mL).
The results from primary tumor tissues revealed an up-regulation of PAI-1 expression in patients that developed metastatic disease. Furthermore, an increase in PAI-1 expression correlated with cell type, displaying an increase in expression from spindle < mixed < epithelioid (p < 0.05). There was also a marked increase in PAI-1 mRNA expression in samples from patients that had extra-ocular extension compared to those that did not. The ELISA results revealed a positive correlation between PAI-1 plasma protein expression and tumor height (n = 11, r = 0.6525, p = 0.0295).
To the best of our knowledge, this is the first time PAI-1 has been shown to correlate with UM prognostic indicators. The use of a serum marker for prognosis is appealing for the management and counseling of UM patients. Further studies with longer follow-up will be able to confirm the utility of PAI-1 to predict metastatic UM.
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