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Prognostic Significance of Nuclear Receptor Coactivator-3 Overexpression in Primary Cutaneous Melanoma

Javier Rangel, Sima Torabian, Ladan Shaikh, Mehdi Nosrati, Frederick L. Baehner, Chris Haqq, Stanley P.L. Leong, James R. Miller, III, Richard W. Sagebiel, Mohammed Kashani-Sabet

From the Auerback Melanoma Research Laboratory, Cutaneous Oncology Program, University of California San Francisco Comprehensive Cancer Center; and the Departments of Dermatology, Pathology, Urology, and Surgery, University of California San Francisco, San Francisco, CA

Address reprint requests to Mohammed Kashani-Sabet, MD, University of California San Francisco Comprehensive Cancer Center, 1600 Divisadero St 2nd Fl, Box 1706, San Francisco, CA 94115; e-mail: kashanim{at}derm.ucsf.edu

PURPOSE: To assess the prognostic significance of nuclear receptor coactivator-3 (NCOA3) overexpression in primary cutaneous melanoma.

PATIENTS AND METHODS: NCOA3 expression was assessed using immunohistochemical analysis of a melanoma tissue microarray (TMA) containing primary melanomas from 343 patients with defined histology and follow-up. The impact of the presence or absence of various prognostic factors on relapse-free survival (RFS) and disease-specific survival (DSS) of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. The impact of presence or absence of various factors on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis.

RESULTS: Increasing degree of NCOA3 expression was significantly predictive of SLN metastasis (P = .013) and the mean number of SLN metastases (P = .031). Kaplan-Meier analysis demonstrated a significant association between NCOA3 overexpression and reduced RFS (P = .021) and DSS (P = .030). Logistic regression analysis revealed increasing degree of NCOA3 expression to be an independent predictor of SLN status (P = .017). Multivariate Cox regression analysis showed the independent impact of NCOA3 expression on RFS (P = .0095) and DSS (P = .021). NCOA3 was the most powerful factor predicting DSS, outperforming tumor thickness and ulceration.

CONCLUSION: These results identify NCOA3 as a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS, and DSS.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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