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Eukaryotic initiation factor is consisted of three major polypeptide subunits (eIF4E, eIF4G, and eIF4A). eIF-4E controls the translation of various malignancy-associated mRNAs which are involved in polyamine synthesis, cell cycle progression, activation of proto-oncogenes, and angiogenesis. Cyclin D1 is also involved in cell cycle progression. This study aimed to assess their expression in lung adenocarcinoma (AdC) and squamous cell carcinoma (SCC) and their association with clinicopathologic variables. In all, 160 resectable lung cancers were studied using a high-density tissue microarray. Two to three cores from each case were arrayed into four blocks using a Beecher system. Immunohistochemistry was performed using an avidin-biotin complex method and monoclonal antibodies against eIF-4E and CycD1. Expression and coexpression of both markers were analyzed against clinicopathologic variables (age, gender, smoking status, performance status, weight loss, histology, grade, stage, and lymph node involvement) and patient survival. There were 147 fully assessable cases for both markers. For eIF-4E, 134 cases (91.2%) showed cytoplasmic over-expression. 82 cases (44.2%) showed nuclear over-expression. For CycD1, 95 cases (64.6%) were positive, and 52 cases (35.4%) were negative. Using Wilcoxon test, cytoplasmic (c-eIF-4E) over-expression correlated with shorter patient survival (p=0.02). Negative nuclear eIF-4E (n-eIF-4E) expression, on the other hand, correlated with advanced stage (IV) and high histologic grade (p=0.001 and 0.017 respectively). C-eIF-4E correlated with n-eIF-4E expression (p=0.001). SCC tended to over-express c-eIF-4E more often compared with AdC, (p=0.0097). There was no significant association between CycD1 alone and any of the clinicopathologic variables. However, over-coexpression of CycD1 and n-eIF-4E was found in early stages of both SCC and AdC. Using Fisher’s exact test, all stage IV cases showed negative staining for CycD1 and n-eIF-4E (p=0.0056). Our study suggests that n-eIF-4E plays an important role in tumor transformation and progression in early stages of lung SCC and AdC. N-eIF-4E and CycD1 play a protective role in advanced stages of these neoplasms. These findings suggest that eIF-4E and CycD1 may by regulated by another factor or factors, or they work, at certain stages, independently in cell cycle progression. Lung SCC may have different tumor transformation mechanism from lung AdC.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]