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

Joseph F. Peevey, Brandon Luke L. Seagle, Kruti P. Maniar, J. Julie Kim*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 14-3-3s 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.

Original languageEnglish (US)
Pages (from-to)42548-42559
Number of pages12
JournalOncotarget
Volume8
Issue number26
DOIs
StatePublished - Jan 1 2017

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Keywords

  • 14-3-3
  • ER
  • Endometrial cancer
  • Obesity
  • PR

ASJC Scopus subject areas

  • Oncology

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