Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Danas Eougken-Evgenios
Dissertation committee:
Θεοχάρης Στμάτιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κορκολοπούλου Πηνελόπη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Καβατζάς Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γακιοπούλου Χαρίκλεια, Καθηγήτρια , Ιατρική Σχολή, ΕΚΠΑ
Νόννη Αφροδίτη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Θυμαρά Ειρήνη, Αναπλ. Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Πατέρας Ιωάννης, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Κλινική σημασία της έκφρασης των υποδοχέων εφρινών (EPH)A2, A4, -A6 στο οφθαλμικό μελάνωμα
Translated title:
Clinical significance of ephrin -a4-a2-a6 in uveal melanoma
Summary:
Uveal melanomas (UMs) comprise the most common primary intraocular malignancies in adults, with the eye representing the second most common site for melanoma, following the skin. They usually appear at older ages than cutaneous melanoma, and their occurrence is associated with a number of risk factors, including the phototype of the patients, the presence of skin and eye nevi, as well as various hereditary syndromes. Prognosis remains poor, with approximately half of the cases presenting with metastatic disease at the time of diagnosis. Regarding disease pathogenesis, there are limited data, according to which both point mutations (GNAQ, GNA11, BAP1, SF3B1 and EIF1AX) and chromosomal abnormalities (monosomy 3, gain of 8q and 6p and loss of 1p) are involved. Erythropoietin-producing human hepatocellular receptors (EPHs) comprise the largest known family of tyrosine receptors, in which, along with their ligands, ephrins, play an important role in a plethora of processes in human physiology, and are implicated in key steps of carcinogenesis. In the present study, EPHA2, EPHA4, and EPHA6 immunohistochemical expressions were investigated in UM tissues and further correlated to a multitude of clinicopathological parameters, including disease stage and patients’ overall survival (OS). High levels of EPHA2 expression were significantly associated with increased tumor vertical thickness (p = 0.03) and the presence of intrascleral involvement (p = 0.05), whereas high EPHA6 nuclear expression was associated with older age at diagnosis (p = 0.03) and absence of retinal detachment (p = 0.05). In a multivariate survival analysis, increased EPHA4 expression was associated with shortened OS along with the presence of metastasis (p < 0.001) and monosomy 3 (p = 0.02). In a separate model, the concurrent overexpression of at least two of the investigated EPHs (HR = 14.7, p = 0.03) also proved to be an independent poor prognostic factor. In conclusion, our results implicate these specific members of the EPHA group as potential biomarkers for disease prognosis as well as possible targets for the development of novel therapeutic interventions.
Main subject category:
Health Sciences
Keywords:
Uveal melanoma, Ephrines, Biomarkers, Cancer, Prognosis
Number of references:
264
