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Eukaryotic Initiation Factor-4E and Cyclin D1 Expression Associated with Patient Survival in Lung Cancer
Authors:Thaer Khoury  Sadir Alrawi  Nithva Ramnath  Qiang Li  Melissa Grimm  Jennifer Black  Dongfeng Tan
Institution:1. Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY;2. Department of Surgical Oncology, University of Florida, Roswell Park Cancer Institute, Jacksonville, Buffalo, NY;3. Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY;4. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY;5. Department of Stress Cell, Roswell Park Cancer Institute, Buffalo, NY;6. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY;7. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston
Abstract:Eukaryotic initiation factor 4E (eIF4E) and cyclin D1, two important factors in cell-cycle progression, play key roles in the carcinogenesis of varied human cancers. However, eIF4E expression in non–small-cell lung cancer (NSCLC) and its association with cyclin D1 has received little investigation. One hundred forty-seven subjects with primary NSCLC, with long-term follow-up and essential clinicopathologic parameters (including age, sex, tumor grade, tumor stage, smoking history, performance status, weight loss, histology grade, and survival data) were evaluated based on expression of eIF4E and cyclin D1. Immunohistochemical analysis was performed using monoclonal antibodies against eIF4E and cyclin D1. While 134 of 147 cases (91%) were positive for eIF4E, 82 of 136 cases (63%) were positive for cyclin D1. Western blot results were consistent with those illustrated by immunohistochemistry. While eIF4E(+) correlated with significantly shorter patient survival (P = .03), cyclin D1(+) correlated with longer patient survival (P = .01). Assessment of coexpression of cyclin D1 and eIF4E shows greater value in determining the prognosis of NSCLC: patients with eIF4E(+)/cyclin D1(?) have poorer outcome, those with eIF4E(?)/cyclin D1(+) have a more favorable outcome, and those with eIF4E(+)/cyclin D1(+) have an intermediate outcome (P = .02). The negative effect on survival in patients with eIF4E(+) suggests its potential prognostic role in NSCLC. These results warrant further investigation to explore the value of eIF4E in identifying patients with aggressive disease for adjuvant treatments.
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