Association between HU177 serum level and prognosis in patients with primary melanoma

Abstract

9044 Background: Cleavage of type IV collagen during extracellular matrix (ECM) remodeling leads to exposure of cryptic regulatory sites within the ECM shown to be involved in tumor angiogenesis. Increased levels of a soluble form of the cryptic epitope HU177 in sera of melanoma patients have been shown to be associated with greater tumor thickness and nodular histological subtype. In this study, we investigate the association between HU177 serum levels and melanoma patients' clinical outcomes. Methods: Sera from 209 patients with primary melanoma prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group at the New York University Langone Medical Center (85 females, 124 males, mean age=58, mean thickness=2.09 mm, Stage I n=140, Stage II n=40, Stage III n=29) were analyzed for HU177 level. HU177 serum levels at the time of diagnosis were then correlated with disease-free survival (DFS) and overall survival (OS). Results: Median follow-up time for survivors was 54.9 months (range 2–81 months). Thirty-eight of the 209 (18%) patients developed recurrences, and 34 of the 209 (16%) patients died during follow-up. HU177 sera levels ranged from 0–139.9 ng/ml (mean=6.2 ng/ml; median=3.7 ng/ml). Because the distribution of HU177 levels was positively skewed, we analyzed the data using the median in addition to the mean. HU177 level > 3.7 ng/ml (the median) was associated with a higher rate of melanoma recurrence (p=0.04) and increasing mortality (p=0.01) in a Kaplan Meier analysis. HU177 remained an independent prognostic factor for DFS and OS when controlling for tumor thickness and histological subtype in multivariate Cox proportional hazards regression models. In the DFS hazard model controlling for tumor thickness and histology, the hazard ratio for HU177 >3.7 ng/ml (the median) was 2.01 (95% CI= 1.002, 4.04; p=0.049). In the OS hazard model controlling for tumor thickness and histology, the hazard ratio for HU177 >3.7 ng/ml (the median) was 2.23 (95% CI=1.06, 4.70; p=0.03). Conclusions: Increased serum level of HU177 identifies a subset of primary melanoma patients with worse prognosis and suggests that anti-angiogenic therapy in the adjuvant setting may be a rational approach. [Table: see text]