title: CD74: a new prognostic factor for patients with malignant pleural mesothelioma.
abstract: BACKGROUND
  The pro-inflammatory cytokine migration inhibitory factor (MIF) and its receptor CD74 have been proposed as possible therapeutic targets in several cancers. We studied the expression of MIF and CD74 together with calretinin in specimens of malignant pleural mesothelioma (MPM), correlating their expression levels with clinico-pathologic parameters, in particular overall survival (OS).
  
  
  METHODS
  Migration inhibitory factor, CD74, and calretinin immunoreactivity were investigated in a tissue microarray of 352 patients diagnosed with MPM. Protein expression intensities were semiquantitatively scored in the tumour cells and in the peritumoral stroma. Markers were matched with OS, age, gender, and histological subtype.
  
  
  RESULTS
  Clinical data from 135 patients were available. Tumour cell expressions of MIF and CD74 were observed in 95% and 98% of MPM specimens, respectively, with a homogenous distribution between the different histotypes. CD74 (P<0.001) but not MIF overexpression (P=0.231) emerged as an independent prognostic factor for prolonged OS. High expression of tumour cell calretinin correlated with the epithelioid histotype and was also predictive of longer OS (P<0.001). When compared with previously characterised putative epithelial-to-mesenchymal transition markers, CD74 correlated positively with tumoral PTEN and podoplanin expressions, but was inversely related with periostin expression.
  
  
  CONCLUSIONS
  High expression of CD74 is an independent prognostic factor for prolonged OS in mesothelioma patients.
authors.affiliation: Division of Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Otterstrom
authors.affiliation: Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Soltermann
authors.affiliation: Division of Thoracic Surgery, University Hospital Zürich, Zürich, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Opitz
authors.affiliation: Laboratory of Molecular Oncology, Clinic for Oncology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Felley-Bosco
authors.affiliation: Division of Thoracic Surgery, University Hospital Zürich, Zürich, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Weder
authors.affiliation: Laboratory of Molecular Oncology, Clinic for Oncology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: R A
authors.initials: RA
authors.lastname: Stahel
authors.affiliation: Division of Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Triponez
authors.affiliation: Division of Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: J H
authors.initials: JH
authors.lastname: Robert
authors.affiliation: Division of Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Serre-Beinier
mesh_terms: D000368:Aged; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D064032:Calbindin 2 / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D014408:Biomarkers, Tumor; D064032:Calbindin 2; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human