Inflammatory marker testing identifies CD74 expression in melanoma tumor cells, and its expression associates with favorable survival for stage III melanoma

Suhendan Ekmekcioglu, Michael A. Davies, Keiji Tanese, Jason Roszik, Myung Shin-Sim, Roland L. Bassett, Denái R. Milton, Scott E. Woodman, Victor G. Prieto, Jeffrey E. Gershenwald, Donald L. Morton, Dave S. Hoon, Elizabeth A. Grimm

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3016-3024
Number of pages9
JournalClinical Cancer Research
Volume22
Issue number12
DOIs
Publication statusPublished - 2016 Jun 15

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Melanoma
Survival
Neoplasms
Nitric Oxide Synthase Type II
Recurrence
Macrophage Migration-Inhibitory Factors
Proteins
Proportional Hazards Models
Research Design
Immunohistochemistry
Observation
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Inflammatory marker testing identifies CD74 expression in melanoma tumor cells, and its expression associates with favorable survival for stage III melanoma. / Ekmekcioglu, Suhendan; Davies, Michael A.; Tanese, Keiji; Roszik, Jason; Shin-Sim, Myung; Bassett, Roland L.; Milton, Denái R.; Woodman, Scott E.; Prieto, Victor G.; Gershenwald, Jeffrey E.; Morton, Donald L.; Hoon, Dave S.; Grimm, Elizabeth A.

In: Clinical Cancer Research, Vol. 22, No. 12, 15.06.2016, p. 3016-3024.

Research output: Contribution to journalArticle

Ekmekcioglu, S, Davies, MA, Tanese, K, Roszik, J, Shin-Sim, M, Bassett, RL, Milton, DR, Woodman, SE, Prieto, VG, Gershenwald, JE, Morton, DL, Hoon, DS & Grimm, EA 2016, 'Inflammatory marker testing identifies CD74 expression in melanoma tumor cells, and its expression associates with favorable survival for stage III melanoma', Clinical Cancer Research, vol. 22, no. 12, pp. 3016-3024. https://doi.org/10.1158/1078-0432.CCR-15-2226
Ekmekcioglu, Suhendan ; Davies, Michael A. ; Tanese, Keiji ; Roszik, Jason ; Shin-Sim, Myung ; Bassett, Roland L. ; Milton, Denái R. ; Woodman, Scott E. ; Prieto, Victor G. ; Gershenwald, Jeffrey E. ; Morton, Donald L. ; Hoon, Dave S. ; Grimm, Elizabeth A. / Inflammatory marker testing identifies CD74 expression in melanoma tumor cells, and its expression associates with favorable survival for stage III melanoma. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 12. pp. 3016-3024.
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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.

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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