Association of body mass index with ER, PR and 14-3-3σ expression in tumor and stroma of type I and type II endometrial carcinoma
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Joseph F. Peevey1, Brandon-Luke L. Seagle2, Kruti P. Maniar1 and J. Julie Kim3
1Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
3Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
J. Julie Kim, email: [email protected]
Keywords: endometrial cancer, PR, ER, 14-3-3, obesity
Received: January 26, 2017 Accepted: April 06, 2017 Published: April 18, 2017
Obesity is a prominent risk factor for endometrial cancer (EC) and can impede on surgical and hormonal treatments. Markers of EC, estrogen receptor (ER), progesterone receptor (PR), phospho(Ser473)-AKT (pAKT) and 14-3-3 sigma (14-3-3σ) were measured in EC tissues in both the tumor and stroma and grouped by body mass index (BMI). Immunohistochemical scoring of 82 cases of Type 1 and Type II EC tissues revealed a significantly increased tumor expression of ER, PR and 14-3-3σ in women with Type I (BMI < 40) as compared to Type II (BMI < 30) EC. With higher BMI, only PR and 14-3-3σ in the tumor epithelium was significantly higher in Type I than Type II. In particular, Type I EC exhibited significantly increased levels of only PR from patients with BMI > 40 compared to BMI < 40. Type II EC showed increased expression of ER in the stroma only between high and low BMI. Analysis of the TCGA RNA-Seq mRNA expression of ER, PR, PIK3CA, PTEN and SFN (gene for 14-3-3σ) confirmed increased PR expression in EC of obese women. In conclusion, ER, PR and 14-3-3σ are differentially regulated in Type I compared to Type II EC while PR is dysregulated in obese women with Type I EC. These findings have potential implications for efficacy of progestin treatment in obese women.
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