Abstract
Purpose :
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. The overall mortality of the disease is estimated to be around 50%despite effective primary tumor treatment. Previous studies have suggested a correlation of tumorigenic and metastatic properties with the presence of cancer stem cells (CSCs). We have previously chararacterized the expression of several CSC markers in UM. In this study, we expanded our analysis to determine the expression of additional stemness markers in primary UM of enucleated eyes and their correlation with metastatic occurence.
Methods :
Six enucleated eyes were immunostained usingantibodies against ABCB5 in addition to our previous study with CD133, ALDH and Nestin, all known markersof cancer stem cells. Intensity and distribution of the staining were evaluated using an established score. Intensity was graded from 0 to 2 (negative, mild and intense) and distribution as focal or diffuse. Through chi square statistical analysis, the development of metastasis was compared to the pattern of staining for each marker.
Results :
All enucleated eyes were positive for at least twomarkers for CSCs. Five cases (83%) were positive for all four markers. ABCB5 was found to stain mildly and more focally for patients with metastasis and more diffuse in those with no metastasis (p=0.0003). The staining was more intense in more pigmented lesions. CD133 wasmainly diffusely stained, with no correlation to metastasis (p=0.078). Staining patterns for both ABCB5 and CD133demonstrated a statistically significant correlation betweenthe development of metastis and a focal staining (p=0.003). Nestin was focally positive in all cases. Epithelioid and cells close to blood vessels had intense staining, and infiltrating lymphocytes were negative.ALDH was positive with an intensity of 1 and focal in four patient samples, and negative in one. Nestin and ALDH showed no correlation between their staining pattern and the development of metastasis.
Conclusions :
In our cohort, Nestin was the most specificmarker for CSCs, followed by ABCB5, CD133 and ALDH. The four markers were positive in almost all cases. As Nestin is positive predominantly in epithelioid cells it could be used as a potential prognostic factor. Larger sample size can better establish a link between the staining patterns of ABCB5 and CD133, and different patient outcomes.
This is a 2020 ARVO Annual Meeting abstract.