Author: Giulia Midena (Italy)
Co-authors: Luisa Frizziero, Alessandra Micera, Graziana Esposito, Elisabetta Pilotto, Edoardo Midena, Raffaele Parrozzani
Purpose
To evaluate, in vivo, the presence of specific aqueous humor (AH) biomarkers in eyes affected by uveal melanoma (UM) and to correlate them with genetic and clinical tumor characteristics.
Setting/Venue
This is a cross-sectional case–control study with prospective enrollment, performed at the Department of Ophthalmology of the University of Padova and IRCCS G.B. Bietti Foundation, Ocular Oncology and Toxicology Unit.
Methods
Thirty-six eyes affected by primary UM underwent full ophthalmic examination, including: ophthalmoscopy, fundus photography, ultrasonography and Spectral Domain OCT. During brachytherapy (Iodine-125) surgical procedure AH sample collection and 25-gauge transscleral fine needle aspiration biopsy (FNAB) were performed. AH samples were analyzed by microarray and western blotting techniques to detect the concentration of selected proteins. Cytologic material underwent fluorescence in situ hybridization for chromosome 3. Tumor thickness and largest basal diameter (LBD) were quantified. Tumors were staged using the 8th AJCC classification. The presence of peritumoral serous retinal detachment was categorized considering the number of retinal sectors involved (less than 1 quadrant; 1 to 2 quadrants; more than 2 quadrants). The AH of thirty-six normal eyes, scheduled for cataract surgery, was used as control. The specific concentration of selected proteins was quantified on the linearized standard curves.
Results
Compared with the control group, significantly higher levels of: SSTR1 (p=0.027), SF3B1 (p=0.026), BAP1 (p=0.012), GNAQ (p=0.024), HMB45 (p=0.017), IL-6 (p=0.049), IL-8 (p=0.007), RANTES (p=0.009), PEDF (p=0.049), Osteopontin (p=0.049), EGF (p=0.042), bFGF (p=0.018), MIF (p=0.008), MCP (p=0.022) were detected in eyes with UM. VEGF concentration difference between the two groups was statistically borderline (p=0.055). Comparison between clinical characteristics and biomarker concentrations showed a positive significant correlation between: tumor thickness and IL-8 (p = 0.032) and VEGF (p = 0.032), degree of serous retinal detachment and IL-6 (p = 0.021), LBD and RANTES (p = 0.031). Monosomy 3 was detected in 17 cases (47%) and disomy 3 in 19 cases (53%). No correlation was found between chromosome 3 status and: tumor dimensions (p= 0.30), and tumor location (ciliary body vs choroid) (p=0.25). Statistically significant higher levels of inflammatory proteins were detected in eyes with monosomy 3 UM (p=0.049).
Conlusions
The presence of selected biomarkers may be identified, in vivo, in the AH of eyes affected by UM. Furthermore, some inflammatory AH biomarkers are specifically correlated to the monosomy 3 pattern, and some clinical characteristics of the tumor itself. These findings not only confirm in vivo the possibilities offered by AH analysis in eyes harbouring a UM, but suggest that AH evaluation may represent the liquid biopsy approach in UM diagnosis and follow-up.
Financial Disclosure
N/A
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