ArticleMolecular oncology2015
PTEN loss is a context-dependent outcome determinant in obese and non-obese endometrioid endometrial cancer patients.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis.Gynecologic oncology · 2016Pooled it
- Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.Nature genetics · 2024Article
- Differences in single gene expression patterns and signaling pathways between Black and White patients in high grade endometrioid endometrial cancer independent of BMI.Gynecologic oncology reports · 2024Article
- Sera Protein Signatures of Endometrial Cancer Lymph Node Metastases.International journal of molecular sciences · 2022Article
- Identification of molecular subtypes premised on the characteristics of immune infiltration of endometrial cancer.Annals of translational medicine · 2022Article
- Identification of altered biological processes in heterogeneous RNA-sequencing data by discretization of expression profiles.Nucleic acids research · 2020Article
- Clinical factors as prognostic variables among molecular subgroups of endometrial cancer.PloS one · 2020Article
- Diagnostic and Prognostic Values of Serum EpCAM, TGM2, and HE4 Levels in Endometrial Cancer.Frontiers in oncology · 2020Article
- Body mass index-associated molecular characteristics involved in tumor immune and metabolic pathways.Cancer & metabolism · 2020Article
- PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?Frontiers in nutrition · 2020Article
- Precise Immunodetection of PTEN Protein in Human Neoplasia.Cold Spring Harbor perspectives in medicine · 2019Review
- Visceral adipose tissue alteration ofAdipocyte · 2019Observational
- Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression.Oncology letters · 2019Article
- Pilot investigation of the mutation profile of PIK3CA/PTEN genes (PI3K pathway) in grade 3 endometrial cancer.Oncology reports · 2019Article
- ZNF277 regulates ovarian cancer cell proliferation and invasion through inhibition of PTEN.OncoTargets and therapy · 2019Article
- Linking obesity-induced leptin-signaling pathways to common endocrine-related cancers in women.Endocrine · 2019Review
- Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Article
- Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification.The journal of pathology. Clinical research · 2017Article
- PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
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.
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