1977

EIF4E

eukaryotic translation initiation factor 4E;EIF4E;eukaryotic translation initiation factor 4E

eIF-4E|eIF-4F 25 kDa subunit|eukaryotic translation initiation factor 4E-like 1|mRNA cap-binding protein

4q23

protein-coding

Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altered in various cancers and has been associated with worse survival. We determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233 breast tumors on tissue microarrays. We analyzed the effects of the IHC expression level on tumor characteristics and patient survival, also with stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained tumors, high level of eIF4E protein expression was associated with features of aggressive tumor phenotype, namely grade, estrogen and progesterone receptor negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and with triple negative subtype (p < 0.001). High eIF4E expression was associated with worse breast cancer-specific survival with a hazard ratio (HR) of 1.99 (95 %

BACKGROUND: Molecular events impact systemic dissemination. Overexpression of eukaryotic initiation factor 4E (eIF4E) has been shown to predict worse clinical outcomes in breast cancer. Node-positive breast cancer patients were specifically studied to determine if eIF4E elevation increases risk for systemic dissemination. STUDY DESIGN: Two hundred two node-positive breast cancer patients were prospectively accrued and treated with standardized treatment and surveillance protocol. tumor eIF4E protein level was quantified by Western blots as x-fold over benign samples from noncancer patients. Primary end point was systemic metastasis. RESULTS: Systemic recurrence was detected in 22.2% of the low eIF4E group, 27.3% of the intermediate group, and 49% of the high group, at a median follow-up of 47 months. A greater risk for systemic metastasis was seen in the high eIF4E group compared with the low group (log-rank test, p = 0.0084). Patients in the high eIF4E group had a 1.5-fold (hazard ratio = 1.52; 95% CI, 1.07-2.17; p = 0.0206) higher risk for systemic metastasis than the low group. Sixty percent of the patients with high eIF4E were observed to have metastasis to multiple sites, compared with 50% in the intermediate group, and 14.5% in the low group (p = 0.02, Fisher's exact test). When patients were segregated based on nodal classification (N1, N2, and N3), eIF4E overexpression continued to be a predictor for systemic dissemination in patients with N1 disease. CONCLUSIONS: High eIF4E is correlated with an increased risk for systemic metastasis in node-positive breast cancer patients. High eIF4E overexpression was associated with a higher incidence of metastasis to multiple sites. Therefore, high eIF4E overexpression appears to be a marker for molecular events that increases risk for systemic dissemination.

AIMS AND BACKGROUND: Mammalian target of rapamycin (mTOR) is one of the serine-threonine protein kinases and plays an important regulatory role in cell growth. Eukaryotic translation initiation factor 4E (eIF4E) and 4E binding protein (4EBP) are the downstream proteins of mTOR signaling pathway and are the most efficient speed regulator of eukaryotic mRNA translation. The aim of the study was to investigate the clinical significance of mTOR, eIF4E and 4EBPs expression in invasive ductal carcinoma. METHODS: Fresh biopsy specimens of invasive ductal carcinoma tissues and normal breast tissues were collected from 45 patients with breast cancer. The expressions of mTOR, eIF4E and 4EBPs in specimens were detected by an immunohistochemical SP method, and the relationship of mTOR, eIF4E and 4EBPS expressions and of their expressions with tumor metastasis were analyzed. RESULTS: expressions of mTOR, eIF4E and 4EBPs in invasive ductal carcinoma were significantly higher than in normal breast tissue (P <0.05). mTOR expression was positively correlated with eIF4E and 4EBP expression in invasive ductal carcinoma (P <0.05). The positive rates of mTOR, eIF4E and 4EBPs in patients with lymph node metastasis were significantly higher than in patients without lymph node metastasis (P <0.05). CONCLUSIONS: Increased expressions of mTOR and eIF4E in invasive ductal carcinoma may be correlated with the occurrence and metastasis of breast cancer.

BACKGROUND AND OBJECTIVE: precious studies proven that the overexpression of eukaryotic translation initiation factor 4E (eIF4E) in a variety of solid tumors has linked with malignant tumorigenesis, invasion and metastasis. The aim of this work is to explore the expression of eIF4E and its clinical significance in non-small cell lung cancer (NSCLC) through immunohistochemical method. METHODS: seventy NSCLC specimens were constructed into tissue microarray, simultaneously took 19 cases adjacent tissues and 20 cases normal lung tissue as control, all performed using immunohistochemistry (Envision). RESULTS: eIF4E expression in NSCLC was significantly higher than that in adjacent tissues and normal lung tissues, statistically significant difference between the groups. The eIF4E positive expression in lymph node metastasis group was significantly higher than that in no-lymph node metastasis. eIF4E protein positive expression of WD/MD cancer tissue was significantly lower than those in PD/ND cancer tissue. There were no significant differences of positive expression of eIF4E with the tumor diameter, age, smoking status, gender of NSCLC patients (P > 0.05). CONCLUSIONS: there were highly over expression rate of eIF4E, and closely correlated with lymphnode metastasis in NSCLC, which implies that the eIF4E expression may be related to tumorgenesis, invasion and metastasis of lung cancer. eIF4E may be a new marker for lung cancer and objective indicators assessing the development of lung cancer.

The ability to define osteosarcoma (OS) patients at greatest risk for metastatic progression and nonresponsiveness to conventional therapy is currently not possible. Such biomarkers are needed to predict overall prognosis, probability of metastases at diagnosis, and response to chemotherapy. The tissue microarray (TMA) serves as a powerful tool for detecting and validating protein biomarkers across a variety of patients. We constructed a novel outcome-linked TMA to add to and address shortcomings of currently available OS tissue resources. To test the use of our TMA, we surveyed the expression of eukaryotic initiation factor 4E (eIF4E) in OS patients using immunohistochemistry. Aberrant regulation of translation initiation is a feature of many cancers. eIF4E is central to initiation of protein synthesis. Its expression and activity have been implicated in tumor formation and potentially malignant and/or metastatic progression in some carcinomas. We found that eIF4E was uniformly expressed in OS patient samples. No association was found between eIF4E and outcome in OS patients. This novel OS TMA provided a facile mechanism to assess the role of a relevant protein biomarker in OS.