Ephrin Receptors (Eph): EphA1, EphA5, and EphA7 Expression in Uveal Melanoma—Associations with Clinical Parameters and Patient Survival

Abstract

Uveal melanoma is the most common primary intraocular malignancy in adults. The development of distant metastases is associated with a poor prognosis. Ephrine receptors (Eph) are the largest subpopulation of tyrosine kinase receptors. They play an important role in processes related to the formation and progression of cancer. The aim of the study was to evaluate the expression of ephrin receptors EphA1, EphA5, and EphA7 in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. The study included 94 previously untreated patients who underwent enucleation due to uveal melanoma. High expression of EphA1 was positively correlated with a smaller tumor size, less frequent extra-scleral extension, lower mitotic activity, and more frequent vitreous hemorrhage. High expression of EphA5 was associated with less frequent chromosome 3 loss, absence of distant metastases, and more frequent vitreous hemorrhage. High expression of EphA7 was associated with a more frequent primary tumor location in the posterior pole. High EphA5 expression was associated with longer overall survival time. The above findings indicate that high expression of EphA1 and EphA5 can be considered a beneficial prognostic factor in uveal melanoma.

Novel Prognostic Immunohistochemical Markers in Uveal Melanoma-Literature Review

“…The same relationship occurs in the case of EGFR (epidermal growth factor receptor), a transmembrane protein that plays a role in epithelial tissue development and homeostasis [40]. High expression of EphA1 correlates with a lower mitotic count, while low expression of NEMO/IKKγ correlates with a higher mitotic count [43,55].…”

“…We found only five studies in the literature in which the expression of specific proteins was related to the status of chromosomes. High EphA5 expression seems to be a favorable prognostic factor as it correlates with less frequent loss of chromosome 3 [43]. In turn, high PARP expression is associated with more frequent loss of chromosome 3 [60].…”

“…Another relationship occurs in the case of EphA1, the erythropoietin-producing human hepatocellular receptor A1, where high expression is associated with a smaller tumor diameter [43]. Thus, high expression is a favorable prognostic factor in this case.…”

“…High EphA1 expression is a favorable prognostic factor as it is associated with a lower incidence of exstrascleral infiltration [43]. In contrast, in the case of Cripto-1 (teratocarcinoma-derived growth factor-1) and Cyclin1, high expression increases the risk of the presence of extrascleral infiltration.…”

“…COX-2 (Cyclooxygenase-2) [34] Enzyme, which catalyze the prostanoid synthesis reaction. 43 High expression correlates with presence of metastasis. c-REL [35] Member of the nuclear factor κB (NF-κB) transcription factor family and an emerging regulator of tumorigenesis.…”