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

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/m), 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 (=+0.48, =+0.50) (<0.05) and nuclear p4E-BP1 (=+0.40, =+0.44) (<0.05); cytoplasmic and nuclear p4E-BP1 were significantly associated with Ki67 (=+0.46, =+0.59) (<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.