Abstract 5220: Increased expression of formyl peptide receptor (FPR) and formyl peptide receptor like-1 (FPRL1) correlates with high-risk clinical/histologic features in melanoma

Abstract

Abstract Melanoma is an aggressive malignancy with a relatively high metastatic rate, responsible for almost 60% of lethal skin tumors. Despite numerous efforts, there is still a need to better understand the molecular pathways involved in malignant melanoma metastasis. FPR and its variant FPRL1, which belong to the GPCR family, have been shown to be involved in metastasis of glioma and ovarian tumor cells via activation of various signaling cascades. It is unknown whether expression of these receptors contributes to the pathogenesis of melanoma. In order to test the hypothesis that aberrant expression of these GPCRs plays a significant role in melanoma progression, we have performed semiquantitative immunohistochemical analysis of FPR and FPRL1 in benign nevi (n=49), primary melanomas with and without metastasis (n=130), and melanoma metastases (n=47 cases). A significant positive correlation was observed between the percentage of positive cells and staining intensity for FPR (p=0.001) and FPRL1 (p=0.009) with progression from benign nevi to primary melanoma. Significantly higher levels of FPR were observed in those lesions having higher Breslow thickness (p=0.044) and ulceration (p=0.019), which are well-established markers of poor clinical outcomes in patients with cutaneous melanoma. On the other hand, lesions showing a radial growth pattern expressed low levels of FPR (p=0.027). A gain in FPRL1 staining was seen in lesions displaying microscopic satellitosis (p=0.051). Disease-specific survival was significantly shorter in patients with increased cytoplasmic expression of FPR (log rank test, p=0.022). Thus, overexpression of FPR and FPRL1 correlates with disease progression and high-risk clinical and histologic features in melanoma. In addition, FPR expression is associated with shorter disease-free survival. Therefore, these markers may be an important therapeutic target in patients with melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5220. doi:10.1158/1538-7445.AM2011-5220