Back to Archived Journals » Current Biomarker Findings » Volume 4

Obesity is associated with higher 4E-BP1 expression in endometrial cancer

Authors Falk Libby E, Azrad M, Novak L, Vazquez AI, Wilson TR, Demark-Wahnefried W

Received 25 August 2013

Accepted for publication 29 October 2013

Published 15 January 2014 Volume 2014:4 Pages 1—7


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Emily Falk Libby,1,* Maria Azrad,1,* Lea Novak,2 Ana I Vazquez,3 Tamara R Wilson,1 Wendy Demark-Wahnefried1

1Department of Nutrition Sciences, 2Department of Pathology, 3Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

*These authors contributed equally to this work

Purpose: Obesity is associated with risk and prognosis of endometrial cancer (EC), and the mammalian target of rapamycin complex 1 (mTORC1) pathway may play an instrumental role. We sought to explore the associations between cellular proliferation, Akt, and 4E binding protein-1 (4E-BP1) (a downstream target of mTORC1), in obese and nonobese women with and without EC.
Methods: Archival tissue-specimens from endometrial biopsies were grouped into two broad categories based on the observed disease behavior and similarities in tissue staining patterns: benign/hyperplasia (without cytologic atypia) (n=18) versus atypia (complex hyperplasia with cytologic atypia)/carcinoma (n=25). The characteristics of the study population, including height and weight to determine body mass index (BMI: kg/m2), were abstracted from medical records. Immunohistochemistry was used to assess the phosphorylated (p)Akt, p4E-BP1, and antigen Ki67.
Results: Cytoplasmic and nuclear pAkt were significantly associated with cytoplasmic p4E-BP1 (ρ=+0.48, ρ=+0.50) (P<0.05) and nuclear p4E-BP1 (ρ=+0.40, ρ=+0.44) (P<0.05); cytoplasmic and nuclear p4E-BP1 were significantly associated with Ki67 (ρ=+0.46, ρ=+0.59) (P<0.05). Compared with the benign/hyperplasia group, the women with atypia/carcinoma had significantly higher cytoplasmic and nuclear p4E-BP1 and Ki67. This staining pattern was similar in obese women; however, in nonobese women, neither cytoplasmic nor nuclear p4E-BP1staining differed between benign/hyperplasia versus atypia/carcinoma.
Conclusion: The activation of 4E-BP1 was higher in the obese women with EC. Adiposity may be a key factor to consider in future studies investigating the role of 4E-BP1 as a biomarker and therapeutic target in EC.

Keywords: mTORC1, immunohistochemistry, gynecologic malignancy, corpus uterine, BMI, biomarker

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]