Expression of eIF4E during head and neck tumorigenesis: possible role in angiogenesis.
OBJECTIVE
The translation initiation factor eIF4E (4E) when overexpressed in mammalian cells results in their oncogenic transformation. 4E facilitates the synthesis of two powerful tumor angiogenic factors (VEGF and FGF-2) by selectively enhancing their translation. 4E is overexpressed not only in all head and neck squamous cell cancers but also in some dysplastic margins. Tumorigenesis in the head and neck is proposed to be a multistep process preceded by clinically evident precancerous lesions. Molecular events underlie the histological changes that herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in angiogenesis.


METHODS
An immunohistochemical analysis with antibodies to 4E, VEGF, and basic (b)-FGF was performed on 115 specimens of the head and neck representing various stages of histological progression of malignancy. This was correlated with mean vessel density (MVD) using factor VIII.


RESULTS
There were 41 cases of hyperplasia and low-grade dysplasia, 40 cases of high-grade dysplasia and 34 cases of cancer. There was a significant increase in the percent of cases expressing 4E from low-grade dysplasia through tumor. However, for VEGF and b-FGF the significant increase was only seen between the tumor group and dysplastic groups and no significant increase was noted between low-grade and high-grade dysplasia There was a significant increase in MVD from low- (10.7+/-1) to high-grade grade dysplasia (18.0+/-2.3). This increase was even more striking for the 4E positive cases.


CONCLUSIONS
4E elevation is correlated with progressive cell transformation in the head and neck. Its correlation with VEGF, b-FGF, and MVD potentiates its possible role in angiogenesis.
Nathan
C O
CO
Department of Otolaryngology/Head & Neck Surgery, Louisiana State University Medical Center and Veterans Administration, Shreveport 71130, USA. cnatha@lsumc.edu
Franklin
S
S
Abreo
F W
FW
Nassar
R
R
de Benedetti
A
A
Williams
J
J
Stucker
F J
FJ
D000912:Antibodies, Neoplasm / Q000235:genetics; D002461:Cell Line, Transformed; D016228:Endothelial Growth Factors / Q000235:genetics*; D039561:Eukaryotic Initiation Factor-4E; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000235:genetics*; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000235:genetics*; D010448:Peptide Initiation Factors / Q000235:genetics*; D011230:Precancerous Conditions; D020033:Protein Isoforms / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000912:Antibodies, Neoplasm; D016228:Endothelial Growth Factors; D039561:Eukaryotic Initiation Factor-4E; D008222:Lymphokines; D010448:Peptide Initiation Factors; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2