Clinical Outcome in Stage I to III Breast Carcinoma and eIF4E Overexpression

Objective The objective of this study is to determine if high eukaryotic initiation factor 4E (elF4E) overexpression (sevenfold elevation or more over benign breast tissue) is associated with a worse clinical outcome. Background Data Dysregulation of cellular functions by selective overexpression of specific proteins can lead to malignant transformation. The overexpression of elF4E preferentially increases translation of mRNAs with long, G-C rich 5'-untranslated regions. Selective gene products, such as tumor neoangiogenic factors, ornithine decarboxylase, and cyclin D1, are upregulated. Methods One hundred fourteen breast specimens were analyzed and elF4E overexpression was quantified by Westem blot analysis. Quantification for elF4E protein level was accomplished using a rabbit anti-elF4E antibody and colorimetric development of Western blots using nitro blue tetrazolium and 5-bromo-4-chloro-3-indolyl phosphate. The blots were scanned and analyzed by densitometry. Treatment, pathologic, and clinical outcome data variables were analyzed. Statistical analysis was performed to determine if elF4E overexpression is associated with breast cancer clinical outcome. Results In the 55 benign specimens, the mean elF4E expression was 1.1 ± 0.4 fold (mean ± standard deviation). All 59 malignant breast carcinoma specimens were noted to have elF4E overexpression (range, 1.9-fold to 30.6-fold), with a mean overexpression of 10.8 ± 6.3-fold. The mean level of elF4E expression in malignant specimens was higher than benign specimens (p < 0.05, unpaired t test). The degree of elF4E overexpression appears to be independent of T and N stage. In the 21 patients with elF4E overexpression of less than sevenfold, there was one cancer recurrence but no cancer-related deaths. In the 38 patients with high elF4E overexpression (sevenfold or more), 14 patients had breast cancer recurrences (p = 0.03, log rank test), of whom 11 have died from the disease (p = 0.04, log rank test). The average follow-up interval in this study was 40 months. Conclusions Patients with stage I to III breast cancer and high elF4E overexpression had a higher rate of cancer recurrence and a higher rate of cancer-related death when compared to similar-stage breast cancer patients with low elF4E overexpression. Therefore, elF4E protein overexpression may be of prognostic value in stage I to III breast carcinoma.