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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4815768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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