Article Text
Abstract
Objectives Investigate the importance of a set of easy accessible biomarkers besides lymphnode(LN) status within the ESMO risk stratification for optimizing adjuvant treatment in endometrial cancer.
Methods Within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), a retrospective multicenter cohort study was performed with a median follow-up of 5.5-years. Immunohistochemical analysis of tumor protein 53(p53), estrogen receptor(ER), progesterone receptor(PR) and L1 cell-adhesion molecule(L1CAM) expression were analyzed on pre-operative specimens. Biomarker expression was related to LN status, defined as positive(N1), negative(N0) or unknown(Nx). Correlations and Cox regression analysis were performed.
Results A total of 763 EC patients were included. Lymphadenectomy was performed in 493(64.6%) patients of whom 53(6.9%) had N1. Adjuvant treatment was applied in 347(46.5%) patients. Abnormal p53(p53-abn) expression was observed in 14.7%, L1CAM expression in 10.4%, loss of ER in 10.0%, and loss of PR in 18.1%. Significant reduced disease specific survival(DSS) and/or recurrence free survival(RFS) was observed within patients with N1 and 53-abn, L1CAM positive expression, or loss of ER/PR. N1 and normal biomarkers show the same prognosis as patients with N0 or Nx, and abnormal biomarkers. In the multivariate Cox regression analysis loss of ER/PR and p53-abn were in addition to the ESMO classification ‘high-intermediate and high’ significantly associated with decreased DSS (HR 2.47[CI 1.20–5.07]p=0.013, HR 2.13[CI 1.02–4.41]p=0.043, HR 3.93[CI 1.98–7.81]p<0.001).
Conclusions We have shown that abnormal biomarker expression in addition to N1 or N0, is highly relevant in survival analysis and could potentially complement the ESMO risk stratification and therefore optimize adjuvant treatment.