TY - JOUR
T1 - Inflammatory marker testing identifies CD74 expression in melanoma tumor cells, and its expression associates with favorable survival for stage III melanoma
AU - Ekmekcioglu, Suhendan
AU - Davies, Michael A.
AU - Tanese, Keiji
AU - Roszik, Jason
AU - Shin-Sim, Myung
AU - Bassett, Roland L.
AU - Milton, Denái R.
AU - Woodman, Scott E.
AU - Prieto, Victor G.
AU - Gershenwald, Jeffrey E.
AU - Morton, Donald L.
AU - Hoon, Dave S.
AU - Grimm, Elizabeth A.
N1 - Funding Information:
This work was supported by the MD Anderson Cancer Center SPORE in Melanoma P50 CA093459 (to S. Ekmekcioglu, M.A. Davies, R.L. Bassett Jr, V.G. Prieto, J.E. Gershenwald, and E.A. Grimm) funded from the NIH, the MD Anderson's Cancer Center Support Grant P30- CA016672 (to E.A. Grimm) funded from the NIH, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to K. Tanese, D.L. Morton, D.S. Hoon, and E.A. Grimm), The University of Texas, M.D. Anderson Cancer Center Melanoma Moon Shots Program (to M.A. Davies, J.E. Gershenwald, and E.A. Grimm), the Miriam and Jim Mulva Foundation, and AIM at Melanoma Foundations. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Publisher Copyright:
©2016 AACR.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - Purpose: Inflammatory marker expression in stage III melanoma tumors was evaluated for association with outcome, using two independent cohorts of stage III melanoma patients' tumor tissues. Experimental Design: Fifteen markers of interest were selected for analysis, and their expression in melanoma tissues was determined by immunohistochemistry. Proteins associating with either overall survival (OS) or recurrence-free survival (RFS) in the retrospective discovery tissue microarray (TMA; n = 158) were subsequently evaluated in an independent validation TMA (n = 114). Cox proportional hazards regression models were used to assess the association between survival parameters and covariates, the Kaplan-Meier method to estimate the distribution of survival, and the log-rank test to compare distributions. Results: Expression of CD74 on melanoma cells was unique, and in the discovery TMA, it associated with favorable patient outcome (OS: HR, 0.53; P = 0.01 and RFS: HR, 0.56; P = 0.01). The validation data set confirmed the CD74 prognostic significance and revealed that the absence of macrophage migration inhibitory factor (MIF) and inducible nitric oxide synthase (iNOS) was also associated with poor survival parameters. Consistent with the protein observation, tumor CD74 mRNA expression also correlated positively (P = 0.003) with OS in the melanoma TCGA data set. Conclusions: Our data validate CD74 as a useful prognostic tumor cell protein marker associated with favorable RFS and OS in stage III melanoma. Low or negative expression of MIF in both TMAs and of iNOS in the validation set also provided useful prognostic data. A disease-specific investigation of CD74's functional significance is warranted, and other markers appear intriguing to pursue.
AB - Purpose: Inflammatory marker expression in stage III melanoma tumors was evaluated for association with outcome, using two independent cohorts of stage III melanoma patients' tumor tissues. Experimental Design: Fifteen markers of interest were selected for analysis, and their expression in melanoma tissues was determined by immunohistochemistry. Proteins associating with either overall survival (OS) or recurrence-free survival (RFS) in the retrospective discovery tissue microarray (TMA; n = 158) were subsequently evaluated in an independent validation TMA (n = 114). Cox proportional hazards regression models were used to assess the association between survival parameters and covariates, the Kaplan-Meier method to estimate the distribution of survival, and the log-rank test to compare distributions. Results: Expression of CD74 on melanoma cells was unique, and in the discovery TMA, it associated with favorable patient outcome (OS: HR, 0.53; P = 0.01 and RFS: HR, 0.56; P = 0.01). The validation data set confirmed the CD74 prognostic significance and revealed that the absence of macrophage migration inhibitory factor (MIF) and inducible nitric oxide synthase (iNOS) was also associated with poor survival parameters. Consistent with the protein observation, tumor CD74 mRNA expression also correlated positively (P = 0.003) with OS in the melanoma TCGA data set. Conclusions: Our data validate CD74 as a useful prognostic tumor cell protein marker associated with favorable RFS and OS in stage III melanoma. Low or negative expression of MIF in both TMAs and of iNOS in the validation set also provided useful prognostic data. A disease-specific investigation of CD74's functional significance is warranted, and other markers appear intriguing to pursue.
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U2 - 10.1158/1078-0432.CCR-15-2226
DO - 10.1158/1078-0432.CCR-15-2226
M3 - Article
C2 - 26783288
AN - SCOPUS:84975070413
SN - 1078-0432
VL - 22
SP - 3016
EP - 3024
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -