Expression of Raf Kinase Inhibitor Protein (RKIP) is a predictor of uveal melanoma metastasis.
Melanoma arising from melanocytes within the choroid is the most frequent primary intraocular neoplasm in adults. It is biologically distinct from cutaneous melanoma by a very strong propensity to metastasize the liver. Raf kinase inhibitor protein is a member of an evolutionarily conserved group of proteins called phosphatidylethanolamine-binding proteins. It is an interacting partner of Raf-1 and a negative regulator of the mitogen-activated protein kinase cascade initiated by Raf-1. Raf kinase inhibitor protein expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. In the present study, we examined the immunohistochemical expression levels of Raf kinase inhibitor protein and phosphorylated Raf kinase inhibitor protein in primary uveal melanoma with and without metastasis, and evaluated their association with other high risk characteristics for metastasis in order to assess whether Raf kinase inhibitor protein and phosphorylated Raf kinase inhibitor protein can be used to predict metastasis. A significant low expression of Raf kinase inhibitor protein was seen in patients with metastasis but not in patients without metastasis. The latter more frequently had a high expression of Raf kinase inhibitor protein. No significant difference was seen in phosphorylated Raf kinase inhibitor protein expression between patients with and without metastasis. Raf kinase inhibitor protein expression is a suitable and easily determinable marker in the primary tumour that could predict the risk of uveal melanoma to metastasize, and hence guide strategies for monitoring and therapy.
Department G.F. Ingrassia, Section of Anatomic Pathology, University of Catania, Italy. rosario.caltabiano@unict.it.
Rosario
R
Caltabiano
Department G.F. Ingrassia, Section of Anatomic Pathology, University of Catania, Italy.
Lidia
L
Puzzo
Department of Human Pathology, Section of Pathological Anatomy, University of Messina, Italy.
Valeria
V
Barresi
Department of Bio-medical Sciences, Section of Physiology, University of Catania, Italy.
Venera
V
Cardile
Department of Bio-medical Sciences, Division of Anatomy and Histology, University of Catania, Italy.
Carla
C
Loreto
Department G.F. Ingrassia, Section of Molecular Biomedicine, University of Catania, Italy.
Marco
M
Ragusa
Department of Ophthalmology, University of Catania, Catania, Italy.
Andrea
A
Russo
Department of Ophthalmology, University of Catania, Catania, Italy.
Michele
M
Reibaldi
Department of Ophthalmology, University of Catania, Catania, Italy.
Antonio
A
Longo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D049488:Phosphatidylethanolamine Binding Protein / Q000096:biosynthesis* / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology*; D000098943:Uveal Melanoma
D014408:Biomarkers, Tumor; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein