FOXO1 expression in uveal melanoma and ocular tissues of normal eyes

Abstract

Purpose: Forkhead transcription factor class O1 (FOXO1) is necessary for the normal development of the vascular system. Loss of FOXO1 may be associated with tumorigenesis and cancer progression. Also, FOXO1 is involved in cancer cell chemoresistance. Our purpose was to evaluate and compare the expression of FOXO1 in eyes with uveal melanoma (UM) to normal eyes.

Methods: Twenty-six eyes with UM and pertinent clinical information were retrieved from the Henry C. Witelson Ocular Pathology Laboratory (McGill University, Canada). Immunohistochemical expression of FOXO1 in eyes harboring UM was compared to 25 normal eyes (>50 years old; obtained from The Eye Bank of Canada). FOXO1 staining was scored by an ocular pathologist according to intensity and extent: low (1), moderate (2), or strong (3) for the former; and less than 50% (1), between 50 and 80% (2), and more than 80% (3), for the latter. Data were then converted to a numeric final score by multiplying the intensity and extent staining scores, resulting in a score ranging from 0 to 9 (0=negative;1-3=weak;4-6=moderate; 7-9=strong). The Student’s t-test was used to determine statistical significance. A Kaplan-Meier survival analysis using the log-rank test was used to evaluate differences in survival curves according to staining score.

Results: FOXO1 was expressed in 57.3% of UM cells. Choroidal and retinal vessels in normal eyes had higher FOXO1 scores compared to tumor harboring eyes (P=0.0001). In UM eyes, tumor cells had higher FOXO1 scores compared to normal choroidal melanocytes (P=0.0001). There was no statistical difference in expression in the other eye structures between the two groups and there was no association between expression of FOXO1 and metastases or FOXO1 and cell type.

Conclusions: Uveal melanoma cells showed higher expression of FOXO1 than normal melanocytes. Due to the evidence that FOXO1 decreases apoptosis via the PI3K/Akt pathway, the higher expression of FOXO1 in melanoma cells may indicate increased cell proliferation and viability of the malignant cells. The low expression of FOXO1 in normal choroidal and retinal vessels in uveal melanoma cases should be further investigated.

Keywords: 744 tumors • 554 immunohistochemistry