4E-BP1 and eIF4E in Uveal Melanoma Associate with Prognosis
MC Dinares, C Parada, T Moline, P Huguet, R Medel, V Peg, J Hernandez-Losa, S Ramon y Cajal. Hospital Universitari Vall d'Hebron, Barcelona, Spain; Fundació, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain
Background: During tumor development regulation of cap-dependent translation is critical to determine the rate of growth and the sensitivity to stimulus like hypoxia, low nutrient concentration and others. This mechanism is tightly controlled by the assembly of the multiprotein complex eIF4F, encompassing among the others eIF4E and eIF4G. eIF4E is sequestered in the cytoplasm by 4E-BP1 and in the nucleus by PML, in both cases rendering eIF4E non-functional. 4E-BP1 is regulated itself by several phosphorylations, controlled by the mTORC1 complex. In this regard, 4E-BP1 has been demonstrating to correlate with poor prognosis and high pathologic rate breast, ovarian and recently in skin melanoma metastasis. The aim of this work is to study the role of these centre of funnel factor in cell signaling in uveal melanoma tumors in order to prove if there is an association with poor prognosis.
Design: Thirty-nine uveal melanomas from enucleated eyes were selected. Immunohistochemistry was performed for 4E-BP1, p4E-BP1, eIF4E, peIF4G, PML and Ki-67.These factors correlated with prognosis and histopathological features of the tumors including size, necrosis and subtype.
Results: From a biological and molecular point of view, a correlation between 4E-BP1 and p4E-BP1 (R2=0,23) was found, as well as p4E-BP1 and eIF4E (R2=0,24) and peIF4G (R2=0,12). Moreover a correlation between p4E-BP1, eIF4E, peIF4G and Ki-67 was detected (R2=0,03; R2=0,01; R2=0,02). Regarding histopathology features, 4E-BP1 expression was associated with intense vascular pattern, p4E-BP1 with larger size (R2=0,06), eIF4E and necrosis and finally Ki-67 with necrosis and also metastasis.
Conclusions: In this study we have observed several correlations between the level of expression of 4E-BP1, p4E-BP1 and eIF4E with size of the tumor, angiogenesis and prognosis. Further studies with a higher number of cases is ongoing to confirm this data.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 256, Wednesday Afternoon