title: Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma.
abstract: Melanoma is a disease that primarily arises in the skin but is a derivative of the neural crest. Eukaryotic translation initiation factor 4E (eIF4E) regulates translation of multiple malignancy-associated mRNAs and is overexpressed in many epithelial tumours. However, expression in human tumours derived from the neural crest is unknown. Here, we determined the association of eIF4E and phospho-eIF4E expression in melanocytic lesions with malignant conversion, metastatic potential and patient survival.
  
  
  
  Archived formalin-fixed, paraffin-embedded surgical specimens from 114 patients with melanocytic lesions were stained immunohistochemically for eIF4E and phospho-eIF4E and evaluated semiquantitatively. The relationship between cytoplasmic and nuclear eIF4E and phospho-eIF4E protein expression, melanocytic lesion subtype and tumour progression was determined. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed.
  
  
  
  Increased eIF4E and phospho-eIF4E expression was highly associated with malignancy (P<0.0001). High nuclear phospho-eIF4E was associated with synchronous or future metastasis (P=0.0059). Kaplan-Meier analyses demonstrated highly significant associations between high histoscores for cytoplasmic and nuclear phospho-eIF4E and reduced survival in all patients (P=0.0003 and 0.0009, respectively).
  
  
  
  Increased melanoma expression of eIF4E and phospho-eIF4E is associated with metastatic potential, reduced survival and increased risk of death.
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071, USA.
authors.forename: Julia H
authors.initials: JH
authors.lastname: Carter
authors.affiliation: Department of Mathematical Sciences, University of Cincinnati, 4512 French Hall, ML 25, Cincinnati, OH 45221, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Deddens
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, 627 South Preston Street, Louisville, KY 40292, USA.
authors.forename: Nelson Reed
authors.initials: NR
authors.lastname: Spaulding
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Lucas
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Colligan
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071, USA.
authors.forename: Thomas Grant
authors.initials: TG
authors.lastname: Lewis
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071, USA.
authors.forename: Elyse
authors.initials: E
authors.lastname: Hawkins
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Jones
authors.affiliation: St Elizabeth Healthcare, Department of Laboratory Medicine, 20 Medical Village Drive, Edgewood, KY 41018, USA.
authors.forename: Jackson O
authors.initials: JO
authors.lastname: Pemberton
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071, USA.
authors.forename: Larry E
authors.initials: LE
authors.lastname: Douglass
authors.affiliation: Eli Lilly & Company, Lilly Corporate Center, DC 0546, Indianapolis, IN 46285, USA.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Graff
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010766:Phosphorylation; D012189:Retrospective Studies; D012694:Serine / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D039561:Eukaryotic Initiation Factor-4E; D012694:Serine