EIF-4E expression is associated with histopathologic grades in cervical neoplasia

Abstract

Translation initiation factor eIF-4E (eukaryotic initiation factor 4E) is a 25 kd messenger RNA cap-binding phosphoprotein and is involved in the initiation of protein synthesis. The expression is known to be elevated in several carcinomas as compared with normal tissues and benign lesions. In the present study, we undertook to determine whether eIF-4E expression is associated with progression in cervical neoplasia. eIF-4E expression was evaluated by immunohistochemistry in 88 formalin-fixed, paraffin-embedded cervical tissues; 10 normal cervical specimens; 19 low-grade cervical intraepithelial neoplasias (CINs); 19 high-grade CINs; and 40 invasive squamous cell carcinomas (ISCCs). In addition, eIF-4E expression was evaluated at the RNA level in fresh frozen cervical carcinoma tissues by real-time quantitative reverse transcriptase polymerase chain reaction. Immunohistochemical staining showed that eIF-4E expression was undetectable in most normal cervical squamous epithelial tissues (90%), but variable staining was observed in the basal layer of all normal endocervical glands. eIF-4E expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with histopathologic grade in the order low-grade CIN < high-grade CIN < ISCC (P < .001) and, in particular, was strongly detected in all ISCC cases. Furthermore, real-time quantitative reverse transcriptase polymerase chain reaction revealed that eIF-4E expression in tumor was significantly enhanced versus normal cervical tissues (P = .037). These results suggest that eIF-4E may play a significant role in tumor progression of cervical neoplasia and may represent useful markers for malignant transformation of cervical squamous cells.