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  • Title: Overexpression of phosphorylated 4E-BP1 predicts for tumor recurrence and reduced survival in cervical carcinoma treated with postoperative radiotherapy.
    Author: Benavente S, Vergés R, Hermosilla E, Fumanal V, Casanova N, García A, Ramón Y Cajal S, Giralt J.
    Journal: Int J Radiat Oncol Biol Phys; 2009 Dec 01; 75(5):1316-22. PubMed ID: 19362787.
    Abstract:
    PURPOSE: To examine the prognostic value of the 4E-BP1 activation state and related upstream/downstream signaling proteins on the clinical outcome of patients with intermediate- or high-risk early-stage cervical carcinoma treated with postoperative radiotherapy and to determine the optimal treatment of early-stage cervical carcinoma. METHODS AND MATERIALS: Immunohistochemical staining was performed on 64 formalin-fixed, paraffin-embedded cervical carcinoma surgical specimens for each protein of the panel (p4E-BP1, phosphorylated mitogen-activated protein kinase, pAkt, vascular endothelial growth factor, KDR, Bcl-2, TP53, receptor for activated C-kinase 1). The expression patterns were related to the clinical data. All patients received postoperative radiotherapy. Concurrent chemotherapy was added if high-risk features were present. The median follow-up was 40 months. RESULTS: Of the 64 patients, 13 received concomitant chemotherapy. p4E-BP1 overexpression in moderate/high-risk early-stage cervical carcinoma correlated significantly with disease-free survival (hazard ratio, 4.39; p = .009) and overall survival (hazard ratio, 4.88; p = .005). Vascular endothelial growth factor, and its receptor KDR, had positive immunoreactivity in all tumor samples. No correlation with clinical outcome was found for the remaining proteins evaluated. CONCLUSION: In this study, moderate/high-risk early-stage cervical carcinoma with low p4E-BP1 expression was highly curable with the current postoperative treatments. For tumors with p4E-BP1 overexpression, new investigational strategies are needed.
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