Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis

Abstract

Uveal melanoma (UM) is the most frequently found primary intraocular tumor, although it accounts for only 5% of all melanomas. Despite novel systemic therapies, patient survival has remained poor. Indeed, almost half of UM patients develop metastases from micro-metastases which were undetectable at diagnosis. Genetic analysis is crucial for metastatic risk prediction, as well as for patient management and follow-up. Several prognostic parameters have been explored, including tumor location, basal dimension and thickness, histopathologic cell type, vascular mimicry patterns, and infiltrating lymphocytes. Herein, the Authors review the available literature concerning cytogenetic prognostic markers and biochemical pathways correlated to UM metastasis development.

Keywords: genetic analyses; metastasis; molecular mechanism; prognostic markers; uveal melanoma (UM).

Graphical Abstract

Red boxes represent high metastatic risk factors; orange box represents intermediate metastatic risk factor (late onset metastasis); green boxes represent low metastatic risk factors.

Figure 1

Haematoxylin-eosin histopathological analysis of uveal melanoma. (With permission of Prof. Giovanni Lanza, Institute of Pathological Anatomy, University of Ferrara).

Figure 2

Malignant choroidal melanoma showing masses of neoplastic epithelioid cells invading a tumor vessel lumen. (Reproduced with permission from Prof. Gallenga P.E., Rass. Ital. Ottal.; published by Clinica oculistica dell’Università di Torino, 1961).