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 facilitate s the synthesis of two powerful tumor angiogenic factors (VEGF and FGF-2) b y 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 under lie the histological changes that;herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in a ngiogenesis, Methods: An immunohistochemical analysis with antibodies to 4E , VEGF, and basic (b)-FGF was performed on 115 specimens of the head and ne ck representing various stages of histological progression of malignancy. T his was correlated with mean vessel density (MVD) using factor VIII. Result s: 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 increa se in the percent of cases expressing 4E from low-grade dysplasia through t umor. However, for VEGF and b-FGF the significant increase was only seen be tween 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. C onclusion: 4E elevation is correlated with progressive cell transformation in the head and neck. Its correlation with VEGF, b-FGF, and MVD potentates its possible role in angiogenesis.