Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma

Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma

Background: 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...

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Bibliographic Details
Published in:British journal of cancer Vol. 114; no. 4; pp. 444 - 453
Main Authors: Carter, Julia H, Deddens, James A, Spaulding IV, Nelson Reed, Lucas, Denise, Colligan, Bruce M, Lewis, Thomas Grant, Hawkins, Elyse, Jones, Jordan, Pemberton, Jackson O, Douglass, Larry E, Graff, Jeremy R
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 16-02-2016
Nature Publishing Group
Subjects:
631/337/458/1733
631/45/612/1230
631/67/1813/1634
692/420/755
Adult
Apoptosis
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Cancer Research
Disease Progression
Drug Resistance
Epidemiology
Eukaryotic Initiation Factor-4E - metabolism
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Kinases
Male
Medical prognosis
Medical research
Melanoma
Melanoma - metabolism
Melanoma - mortality
Melanoma - pathology
Metastasis
Molecular Diagnostics
Molecular Medicine
Mutation
Oncology
Phosphorylation
Retrospective Studies
Serine - metabolism
Skin cancer
Tumors
United States > US
eIF4E
malignant melanoma
phospho-eIF4E
malignant progression
survival
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Summary:Background: 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. Methods: 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. Results: 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). Conclusions: Increased melanoma expression of eIF4E and phospho-eIF4E is associated with metastatic potential, reduced survival and increased risk of death.
Bibliography:Current address: Biothera Pharmaceutical Inc., Eagan, MN, USA.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2015.450