PTEN loss is a context-dependent outcome determinant in obese and non-obese endometrioid endometrial cancer patients Academic Article uri icon

Overview

MeSH Major

  • Carcinoma, Endometrioid
  • Endometrial Neoplasms
  • Ideal Body Weight
  • Obesity
  • PTEN Phosphohydrolase

abstract

  • Endometrial cancer incidence is increasing, due in part to a strong association with obesity. Mutations in the phosphatidylinositol 3-kinase (PI3K) pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid adenocarcinomas, the most common form of endometrial cancer. We sought to determine the impact of PI3K pathway alterations on progression free survival in a cohort of endometrioid endometrial cancers. Prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss by immunohistochemistry, was explored in the context of patient body mass index. Reverse-phase protein arrays were utilized to assess protein expression based on PTEN status. Among 187 endometrioid endometrial cancers, there were no statistically significant associations between PFS and PIK3CA, PIK3R1, PTEN mutation or loss. When stratified by body mass index, PTEN loss was associated with improved progression free survival (P < 0.006) in obese (body mass index ≥ 30) patients. PTEN loss resulted in distinct protein changes: Canonical PI3K pathway activation was observed only in the non-obese population while decreased expression of β-CATENIN and phosphorylated FOXO3A was observed in obese patients. These data suggest the impact of PTEN loss on tumor biology and clinical outcomes must be interpreted in the context of body mass index, and provide a potential explanation for discrepant reports on the effect of PTEN status and obesity on prognosis in endometrial cancer. This reveals a clinically important interaction between metabolic state and tumor genetics that may unveil the biologic underpinning of obesity-related cancers and impact ongoing clinical trials with PI3K pathway inhibitors.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4584169

Digital Object Identifier (DOI)

  • 10.1016/j.molonc.2015.04.014

PubMed ID

  • 26045339

Additional Document Info

start page

  • 1694

end page

  • 703

volume

  • 9

number

  • 8