Abstract #5558: Translation initiation factor eIF4E increases during uterine cervical cancer progression to metastasis and is correlated with cell proliferation

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO The eukaryotic translation initiation factor 4E (eIF4E) is frequently overexpressed in human cancers. In experimental models, enhanced eIF4E function selectively increases translation of mRNAs involved in tumor growth, angiogenesis, and cell survival, thereby driving cellular transformation, tumorigenesis and metastatic progression. Here we examined expression of eIF4E in relation to cell proliferation during tumor progression in human uterine cervical cancer. Archived tissues (N=229) from 121 patients were studied by immunohistochemistry (IHC) using mouse monoclonal antibodies to eIF4E and Ki 67. The series of archived tissues included normal tissues from patients with and without cancer, mild dysplasia (CIN), carcinoma in situ (CIS), invasive cervical cancer (CxCa) and metastatic CxCa. Both cytoplasmic and nuclear eIF4E stain was evaluated semi-quantitatively for the stain intensity (I) and area of tissue stained (A) and the histoscores (HS) were calculated (HS = I x A). Proliferation was quantified by counting Ki 67 labeled nuclei in ten 40X microscopic fields per specimen. The significance of the difference in means between stages of tumor progression was determined by differences of least squares means using the Tukey-Kramer adjustment. The Spearman Correlations were determined for the relationship between proliferating cells/field and eIF4E staining, as well as between these markers and tumor progression. In normal cervix, Ki 67 labeling was predominantly in the parabasal layer (with a few stained nuclei in the basal layer). eIF4E stain was predominantly in the parabasal layer, with some stain also in the basal and intermediate cell layers. In CIS, Ki 67 labeling and eIF4E staining were found scattered throughout the entire thickness of the epithelium. In invasive and metastatic CxCa, Ki 67 labeling and eIF4E staining were found uniformly throughout the tumors. The Spearman Correlation p- values were <0.0001 for correlations between CxCa progression and cytoplasmic eIF4E histoscores and between CxCa progression and proliferating cells/field. Proliferating cells/field and eIF4E were also highly correlated (p<0.0001). Proliferating cells/field, as well as both nuclear and cytoplasmic eIF4E stain were significantly increased in invasive and metastatic CxCa compared to normal tissue (p<0.0001). Because of the strong association of eIF4E with cell proliferation, as well as with progression of cervical cancer to metastasis, these data strongly support the notion that eIF4E could be a therapeutic target for treatment of advanced CxCa. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5558.