A complex role of insulin-like growth factor binding proteins (IGFBPs) in melanoma.

9064 Background: Preclinical data suggest that IGFBP4 inhibits melanoma (MM) angiogenesis and tumor growth, while IGFBP3 exhibits both growth-stimulatory and inhibitory activities in different solid tumors. Given the active development of anti-IGF targeted therapy, currently in Phase I and II clinical trials, we aimed to better define a subset of MM patients (pts) who may benefit from anti-IGF targeted therapy by examining both IGFBP4 and IGFBP3 expression in MM tissues and shedding in sera.,132 MM pts [72 primary (Pri), 60 metastatic (Met)] were prospectively enrolled in the NYU Interdisciplinary Melanoma Cooperative Group (64 Male, 68 Female; median age 56). We used immunohistochemistry to assess tumor IGFBP4 and IGFBP3 protein expression (R&D Systems), and ELISA assays (DSL, Inc.) for sera concentration of IGFBP4 and IGFBP3. Wilcoxon rank-sum tests and Spearman-rank correlation coefficients were used where appropriate. We examined the correlation between IGFBPs, recurrence, and overall survival (OS).,IGFBP4 tumor expression was significantly greater in Pri vs. Met pts (median=70% vs. median=10%, respectively, p=0.01). While median IGFBP3 tumor expression was 90% in Met pts vs. 80% in Pri pts, the difference was statistically significant (p=0.039). No significant difference in median IGFBP4 sera concentration was observed between Pri and Met pts (37.2 ng/ml vs. 41.2 ng/ml, respectively, p=0.26). A trend for greater IGFBP3 sera concentration was observed in Met versus Pri pts (median=4.9 mg/ml vs. median=3.4 mg/ml, respectively, p=0.09). The correlation coefficient between IGFBP4 and IGFBP3 tumor expression was 0.29 in Pri pts (p=0.03) and 0.29 in Met pts (p=0.10). There were no associations between IGFBP4 or IGFBP3 and recurrence in Pri pts [median follow up (FU)=30.6m], or with OS in Met pts (median FU=21.8m).,Our clinical data suggest complex regulation of IGFBPs in MM and support the interplay of IGFBP3 and IGFBP4 in MM progression. Data also suggest that the tissue expression of both IGFBP3 and IGFBP4 may be more clinically relevant than their sera shedding. Data do not support a prognostic role of measuring IGFBP4 and IGFBP3 in MM pts. No significant financial relationships to disclose.