Abstract 596: Differential cellular localization of Ephrin receptor tyrosine kinase B4 (EphB4) in melanoma progression

Abstract

Abstract Background: Melanoma is an aggressive cancer with high metastatic potential, and is the most lethal skin malignancies. Ephrin receptor tyrosine kinase B4 (EphB4) modulates diverse physiologic and developmental processes, and may play an important role in melanoma tumorigenesis. In addition, Mertens-Walker et al., reported nuclear translocalization of EphB4 and hypothesized that it may directly regulate gene expression contributing to more aggressive biologic behavior in prostate cancer (Cancer Res 2011; 71 (8 Suppl): Abstract nr 1085). It is unknown whether differential cellular expression of EphB4 contributes to the pathogenesis of melanoma. Methods: To explore the role of EphB4 in melanomagenesis, we have performed semiquantitative immunohistochemical analysis of EphB4 expression as measured by percentage and intensity of cells immunoreactive with anti-EphB4 in melanocytic nevi (n = 59), primary melanomas without metastasis during follow-up (n = 22), primary melanomas with metastasis (n = 17), and metastatic melanoma (n = 32). Results: Melanocytic nevi had significantly higher nuclear EphB4 expression (p = 0.007) and lower cytoplasmic EphB4 expression (p = 0.002) when compared to all categories of melanoma. In fact we observed a dramatic decrease in nuclear EphB4 expression in metastatic melanoma compared to melanocytic nevi (p = 0.0009). In contrast, compared to melanocytic nevi, cytoplasmic expression for EphB4 were higher in primary melanoma (p = 0.005) as well as in melanoma metastases (p = 0.03). Although there was no significant difference in nuclear or cytoplasmic EphB4 expression between primary melanomas with or without metastasis, primary melanomas without metastasis showed significantly higher number of tumor cells having intense nuclear immunoreactivity for EphB4 protein than did metastatic melanomas (p = 0.006). Conclusion: In conclusion, our data indicated that there is a gradual loss of nuclear EphB4 protein as well as increase in the levels of cytoplasmic expression of EphB4 protein associated with melanomagenesis. In addition, our results suggest a potential role for EphB4 as a therapeutic target in melanoma. Citation Format: Nitin Chakravarti, Jonathan L. Curry, Roland L. Bassett, Victor G. Prieto. Differential cellular localization of Ephrin receptor tyrosine kinase B4 (EphB4) in melanoma progression. [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 596. doi:10.1158/1538-7445.AM2015-596