Progressive amplification and overexpression of the eukaryotic initiation factor 4E gene in different zones of head and neck cancers.

Overview

abstract

PURPOSE: Eukaryotic initiation factor 4E (eIF4E) binds to mRNA as the initial rate-limiting step in protein synthesis. Amplification and overexpression of the eIF4E gene has been associated with malignant transformation. The objectives of this study were to 1) quantify the eIF4E gene in head and neck squamous cell carcinoma (HNSCC) specimens, 2) quantify eIF4E protein elevation and examine its association with eIF4E gene amplification, and 3) determine whether there is progression in eIF4E gene amplification and protein overexpression in the tumor-free resection margin, the transition zone, and the tumor core of HNSCC specimens. MATERIALS AND METHODS: Eighteen HNSCC specimens were divided into three zones: 1) tumor core; 2) transition zone; and 3) "tumor-free" margin. Competitive polymerase chain reaction was performed to determine eIF4E gene copy number. eIF4E protein expression was quantified using Western blot analysis. RESULTS: All 18 HNSCC specimens tested had significant eIF4E gene amplification (4.3+/-1.2; P < .05). In contrast, none of the 10 benign specimens from noncancer patients had any eIF4E gene amplification (1.1+/-0.5). In the 12 HNSCC specimens examined for the three zones, the tumor core and transition zone showed eIF4E gene amplification (5.2+/-1.1 and 3.5+/-0.9, respectively) compared with the "tumor-free" margin (2.1+/-1.1; P < .05). The tumor core and transition zone showed significant efF4E protein elevation (15.5+/-9.3, 4.4+/-4.6, respectively) compared with the "tumor-free" margin (0.9+/-0.5, P < .05). CONCLUSIONS: The eIF4E gene is amplified and overexpressed in HNSCC. Amplification and elevation of eIF4E were highest in the tumor core, intermediate in the transition zone, and lowest in the tumor-free margin. There appears to be progression of eIF4E gene amplification and overexpression from the "tumor-free" margin to the tumor core.