EC is common and incidence has increased by 65% in 40 years. There are no validated biomarkers or approved targeted therapies in clinical use. This study evaluates a novel biomarker panel in EC by correlating clinico-pathological features and tumour tissue expression levels of p53, PTEN, phospho-P70S6K (pS6), phospho-Stathmin (pSTMN). pS6 and pSTMN activity is influenced by PI3K/Akt pathway activation which frequently occurs in EC.
The 144 EC patients who had primary surgery from January 2006 to December 2010 at University College London Hospital were retrospectively identified and included in this analysis. Patient characteristics are shown in Table 1. Antibodies for p53, PTEN, pS6 and pSTMN were optimised for use in this study. IHC was performed on surgical resection specimens. Standard scoring methods incorporating percentage of cells stained and staining intensity were applied.
Univariate analysis for disease specific survival (DSS) showed, as expected, non-endometrioid histology, grade 3 tumour, presence of lymphovascular invasion (LVI) or myometrial invasion (MI) and advanced International Federation of Gynaecology and Obstetrics (FIGO) stage conferred poor DSS. The overexpression of p53 and pSTMN was also associated with poor DSS. In multivariate analysis grade 3 histology, MI, p53 and pSTMN overexpression were the only factors that remained significantly associated with poor DSS.
Cox proportional hazard regression model comparing clinico-pathological features and biomarker expression with DSS. NA-Not applicable. HR-Hazard ratio. CI- Confidence interval.
|Variable||Categories||Univariate Analysis||Multivariate Analysis|
|n||Deaths||HR (95% CI)||p value||HR(95% CI)||p value|
|Age||>65 ≥65||59 85||7 17||1.91 (0.79-4.62)||0.15||3.43 (0.33-35.14)||0.3|
|Histological sub-type||Endometrioid Non-endometrioid||128 16||16 8||4.90 (2.09-11.48)|
We demonstrate for the first time that p53 and pSTMN overexpression are independent predictors of DSS in EC and may be useful prognostic biomarkers. Overexpression of pSTMN may predict sensitivity to PI3K pathway inhibitors in EC. Prospective evaluation is warranted in clinical studies.
Clinical trial identification
Legal entity responsible for the study
UCL Cancer Institute
UCL Cancer Institute
All authors have declared no conflicts of interest.