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

Libby, Emily Falk; Azrad, Maria; Novak, Lea; Vazquez, Ana I.; Wilson, Tamara R.; Demark-Wahnefried, Wendy
January 2014
Current Biomarker Findings;2014, Vol. 4, p1
Academic Journal
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 (β=+0.48, β=+0.50) (P<0.05) and nuclear p4E-BP1 (β=+0.40, β=+0.44) (P<0.05); cytoplasmic and nuclear p4E-BP1 were significantly associated with Ki67 (β=+0.46, β=+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.


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