Abstract 4963: Prognostic significance of the expression of nuclear EIF5A2 in human melanoma

Abstract

Abstract Eukaryotic translation initiation factor 5A2 (EIF5A2) is an oncogene that is upregulated in several different cancers. We previously showed that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with melanoma patient survival. In this study, we used immunohistochemistry and tissue microarray (TMA) using a large number of melanocytic lesions (n = 459) to examine the expression profile of nuclear EIF5A2 in melanoma progression in addition to the correlation between nuclear EIF5A2 expression and melanoma patient survival. We found that nuclear EIF5A2 expression was significantly upregulated in primary melanomas compared with normal nevi and dysplastic nevi, as well as in metastatic melanomas compared with primary melanomas, normal nevi and dysplastic nevi. Nuclear EIF5A2 expression had a significant inverse correlation with overall and disease-specific 5-year survival of all and primary melanoma patients. Nuclear EIF5A2 expression was also significantly correlated with melanoma thickness and AJCC stages, suggesting the possible role of nuclear EIF5A2 in melanoma cell invasion. We then investigated the correlation between the expression of nuclear EIF5A2 and MMP-2 which is one of the important factors for promoting cancer cell invasion. Nuclear EIF5A2 expression and strong MMP-2 expression were directly correlated as well, and their concurrent expression was significantly associated with worse overall and disease-specific 5-year survival of all and primary melanoma patients. We also studied the correlation between nuclear and cytoplasmic EIF5A2 expression and found that they were significantly correlated, and simultaneous expression of both was significantly associated with poor overall and diseases-specific 5-year survival of all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear expression of EIF5A2 was an adverse independent prognostic factor for melanoma patients. In conclusion, we for the first time demonstrated the nuclear expression of EIF5A2 as an independent prognostic marker in melanoma and its role in melanoma progression and patient survival. As a result, nuclear EIF5A2 may have the potential to serve as a therapeutic marker for melanoma. Citation Format: Shahram Khosravi, Magdalena Martinka, Christopher J Ong. Prognostic significance of the expression of nuclear EIF5A2 in human melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4963. doi:10.1158/1538-7445.AM2015-4963