title: Obesity is associated with higher 4E-BP1 expression in endometrial cancer.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Emily Falk
authors.initials: EF
authors.lastname: Libby
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Azrad
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Lea
authors.initials: L
authors.lastname: Novak
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Vazquez
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Tamara R
authors.initials: TR
authors.lastname: Wilson
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Demark-Wahnefried
keywords: BMI; biomarker; corpus uterine; gynecologic malignancy; immunohistochemistry; mTORC1