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
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