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


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.


CONCLUSIONS
These results identify NCOA3 as a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS, and DSS.
Rangel
Javier
J
Auerback Melanoma Research Laboratory, Cutaneous Oncology Program, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA 94115, USA.
Torabian
Sima
S
Shaikh
Ladan
L
Nosrati
Mehdi
M
Baehner
Frederick L
FL
Haqq
Chris
C
Leong
Stanley P L
SP
Miller
James R
JR
Sagebiel
Richard W
RW
Kashani-Sabet
Mohammed
M
D014408:Biomarkers, Tumor; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D015534:Trans-Activators; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3