NCOA3: A molecular prognostic marker for melanoma
8007 Background: Nuclear receptor coactivator-3 (NCOA3, also known as AIB1 or SRC-3), a member of the steroid receptor coactivator 1 family, has been shown to be amplified in human breast cancer. We recently identified NCOA3 as differentially expressed in metastatic melanomas by gene expression profiling, suggesting its role as a possible molecular prognostic factor. In this study, we assessed the prognostic significance of NCOA3 expression in a large melanoma patient cohort using tissue micro-arrays (TMAs). Methods: We used a commercially available antibody against NCOA3 to perform immunohistochemical analysis of NCOA3 expression in TMAs containing primary melanoma specimens from 353 patients seen at the UCSF Melanoma Center. Cases included clinicopathologic information (e.g., age, sex, tumor location, tumor thickness, Clark level and ulceration), as well as sentinel lymph node (SLN) status, and information regarding relapse-free (RFS) and disease-specific (DSS) survival. NCOA3 expression was assessed on a 4-point scale (0–3) by an observer blinded to patient outcomes. Results: High NCOA3 expression was significantly predictive of SLN metastasis by univariate logistic regression (p=0.015), and associated with a higher mean positive SLN count (p=0.03, Le test). Kaplan-Meier analysis demonstrated a significant association between increased NCOA3 expression and reduced RFS as well as DSS (p=0.024, and p=0.031 by log-rank test, respectively). Multivariate step-wise logistic regression analysis of 12 factors revealed NCOA3 expression, along with tumor thickness, age, vascular involvement, and Clark level to be independent predictors of SLN status. Multivariate Cox regression analysis showed the independent impact of NCOA3 expression on RFS and DSS with the inclusion of the AJCC factors tumor thickness, ulceration, Clark level, tumor location, patient age and sex. Conclusions: These results reveal NCOA3 to be a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS and DSS. No significant financial relationships to disclose.