title: Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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. Clin Cancer Res; 22(12); 3016-24. ©2016 AACR.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. sekmekcioglu@mdanderson.org egrimm@mdanderson.org.
authors.forename: Suhendan
authors.initials: S
authors.lastname: Ekmekcioglu
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanese
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jason
authors.initials: J
authors.lastname: Roszik
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California.
authors.forename: Myung
authors.initials: M
authors.lastname: Shin-Sim
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Denái R
authors.initials: DR
authors.lastname: Milton
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Woodman
authors.affiliation: Department of Pathology and Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California.
authors.forename: Dave S
authors.initials: DS
authors.lastname: Hoon
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. sekmekcioglu@mdanderson.org egrimm@mdanderson.org.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grimm
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology*; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D014408:Biomarkers, Tumor; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; C045084:invariant chain; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human