[HTML][HTML] Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma
JH Carter, JA Deddens, NR Spaulding IV… - British journal of …, 2016 - nature.com
JH Carter, JA Deddens, NR Spaulding IV, D Lucas, BM Colligan, TG Lewis, E Hawkins…
British journal of cancer, 2016•nature.comBackground: 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 …
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 …
Abstract
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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