Expression of Eukaryotic Translation Initiation Factors 4E and 2 α Correlates with the Progression of Thyroid Carcinoma

Abstract

Cell growth and proliferation depend on protein synthesis that is regulated, in part, by two eukaryotic translation initiation factors, eIF-4E and eIF-2α. These factors are transiently increased as normal cells respond to growth factors and are constitutively elevated in transformed cells. In cultured cells, eIF-4E facilitates cell cycle progression by increasing the expression of cell cycle promoting proteins including cyclin D1. Our previous study revealed elevated cyclin D1 expression in histologically more aggressive thyroid carcinomas as compared to conventional papillary carcinoma. We hypothesized that the increased cyclin D1 expression might correlate with increased eIF-4E expression. We, therefore studied the expression of eIF-4E by immunohistochemistry in 25 cases of conventional papillary carcinoma(CPC) and 28 cases of aggressive thyroid carcinomas (ATC), the latter included 11 tall cell/columnar cell variant of papillary carcinoma, 5 insular carcinomas, and 12 anaplastic carcinomas. We also analyzed the expression of eIF-2α in the same samples as this factor is usually regulated similarly to eIF-4E in cell culture models. Of the 25 CPC, 13 were eIF-4E positive (11 weakly and 2 strongly), and 19 were eIF-2α positive (14 weakly and 5 strongly). Conversely, of the 28 ATC, 25 were eIF-4E positive (4 weakly and 21 strongly), and 23 were eIF-2α positive (4 weakly and 19 strongly). There was a significantly increased expression of both eIF-4E (p < 0.001) and eIF-2α (p < 0.001) in ATC compared to CPC, suggesting that these translation initiation factors may play a role in the progression of thyroid cancer.