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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815768/
https://www.ncbi.nlm.nih.gov/pubmed/26882068
http://dx.doi.org/10.1038/bjc.2015.450
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author 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
author_facet 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
author_sort Carter, Julia H
collection PubMed
description 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.
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spelling pubmed-48157682017-02-16 Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma 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 Br J Cancer Molecular Diagnostics 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. Nature Publishing Group 2016-02-16 2016-02-04 /pmc/articles/PMC4815768/ /pubmed/26882068 http://dx.doi.org/10.1038/bjc.2015.450 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Molecular Diagnostics
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
Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma
title Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma
title_full Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma
title_fullStr Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma
title_full_unstemmed Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma
title_short Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma
title_sort phosphorylation of eif4e serine 209 is associated with tumour progression and reduced survival in malignant melanoma
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815768/
https://www.ncbi.nlm.nih.gov/pubmed/26882068
http://dx.doi.org/10.1038/bjc.2015.450
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