Abstract LB-517: EIF5A2, A downstream target of PI3K/Akt pathway, Is an adverse prognostic marker of melanoma patient survival by increasing cell invasion

Human cutaneous melanoma is a life-threatening skin cancer due to its invasive nature and high metastatic potential, leading to poor prognosis for melanoma patients. However, the mechanisms for melanoma invasion and metastasis are poorly understood. Human eukaryotic translation initiation factor 5A2 (EIF5A2) has been shown to be associated with tumor progression in multiple types of cancers. We examined EIF5A2 expression in 459 melanocytic lesions at different stages using tissue microarray and immunohistochemistry and analyzed the correlations between EIF5A2 expression and clinicopathologic parameters and patient survival. We found that positive EIF5A2 staining was significantly increased in primary melanomas compared to dysplastic nevi (P=0.002), and further increased in metastatic melanomas (P=0.036). EIF5A2 expression was correlated with melanoma thickness (P=0.0004) and was inversely correlated with overall and disease-specific 5-year survival of primary (P=0.008 and 0.007, respectively), especially low-risk (≤2.0mm) melanoma patients (P=0.026 and 0.044, respectively). We also examined the correlation between EIF5A2 and p-Akt protein expression and their role in regulating melanoma cell invasion. Combining the TMA data sets for EIF5A2 and p-Akt, we found that positive EIF5A2 staining directly correlated with strong p-Akt expression (P=0.026). Additionally, overexpression of PTEN or inhibition of p-Akt or ILK significantly reduced EIF5A2 expression. EIF5A2 overexpression also increased melanoma cell invasion and MMP-2 activity. We for the first time showed that the expression of EIF5A2, a downstream target of PI3K/Akt pathway, is significantly increased during melanoma invasion and is inversely correlated with patient survival, suggesting that EIF5A2 may be used as a potential therapeutic target for melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-517. doi:1538-7445.AM2012-LB-517