Abstract A27: Analyses of the level of liver borne growth factors, IGF-1 and HGF in metastatic and non-metastatic uveal melanoma patient serum: Correlation with outcome

Abstract

Abstract Background: Uveal melanoma arises from melanocytes in the uveal tract of the eye and is biologically different from cutaneous melanoma due to different genetic alterations and a propensity to metastasize to the liver. We hypothesize that growth factors synthesized in liver can play a significant role in this preferential homing of uveal melanoma metastasis. It is critical to explore the factors that can contribute to liver metastasis and identify targets. Further exploring the means to blocking them in a timely fashion is of high therapeutic value. IGF-1 (insulin like growth factor -1) and HGF (hepatocyte growth factor) are two major growth factors secreted from liver. The corresponding receptors, c-Met and IGF-1R have been detected in uveal melanoma tumors and also high protein expression was shown to be associated with poor survival. Therefore we initiated a study to determine the level of serum IGF-1 and HGF at sequential time points for primary and metastatic uveal melanoma patients, with the aim to test for correlation with clinical outcomes. Methods: Commercially available ELISA kits (Quantikine ELISA kits from R&D) were used to measure the levels of IGF-1 and HGF in the serum of 12 uveal melanoma patients at different time points of their treatment and follow up at MD Anderson Cancer Center as a discovery cohort. Blood was drawn at first visit and then at surgery (if relevant) and post-surgery check up, followed by every six month visits or sooner. Serum was isolated from each blood draw and stored at -80 degrees until analysis. At the time of analysis, the serum samples were thawed overnight and used directly in ELISA for HGF and for the IGF-1 with pre-treatment to release the active IGF-1. Patients with detection of metastasis were followed after the diagnosis of metastasis. We compared six patients with metastasis with six others that were free of metastasis at last contact. The serum levels of IGF-1 and HGF were tabulated for each patient and each blood draw, and analyses initiated to test if the levels of IGF-1 or HGF in patients vary at baseline or over time relative to the outcome. Results: We observed a significantly higher level of serum HGF in all 12 patients in this study as compared to the reported normal levels in healthy individuals. Preliminary analyses do not point to an obvious pattern of IGF-1 or HGF serum levels or changes in levels that vary between the metastatic and non-metastatic patients over time. A drawback of the study is the small sample size. Another concern is the dynamic nature of the protein expression, which are being currently investigated. These studies would support additional analysis, and possibly more sensitive and selected marker tests. Supported by the MD Anderson Cancer Center SPORE in Melanoma P50 CA093459, the MD Anderson's Cancer Center Support Grant P30- CA016672, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and funds from the Polo on the Prairie event. Citation Format: Chandrani Chattopadhyay, Junna Oba, Bita Esmaeli, Julie A. Ellerhorst, Elizabeth A. Grimm. Analyses of the level of liver borne growth factors, IGF-1 and HGF in metastatic and non-metastatic uveal melanoma patient serum: Correlation with outcome. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A27.