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295 The importance of biomarker expression in addition to lymph node status in the ESMO risk stratification of endometrial cancer
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  1. S Vrede1,
  2. W Van Weelden1,
  3. N Visser2,
  4. L van der Putten1,
  5. J Bulten1,
  6. K van de Vijver3,
  7. A van der Wurff4,
  8. M Snijders5,
  9. H Vandevelde6,
  10. C Reijnen1 and
  11. J Pijnenborg1
  1. 1Department Obstetrics and Gynaecology, Radboudumc, Netherlands
  2. 2Department of Pathology, Stichting PAMM, Netherlands
  3. 3Department of Pathology, Radboudumc, Netherlands
  4. 4Department of Pathology, Ghent Unisversity Hospital, Belgium
  5. 5Department Obstetrics and Gynaecology, CWZ, Netherlands
  6. 6Department of Pathology, Elisabeth-Tweesteden Hospital, Netherlands

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).

Abstract 295 Figure 1

A-D: A. Kaplan Meier form the ESMO risk classification system. B. Kaplan Meier lymph node (LN) status including p53 status. Recurrence free survival (RFS) for p53-abn and p53-wt with lymph node positive (NI), lymph node negative (NO) and unknown lymph nodal status (Nx). C. Kaplan Meier LN status including LICAM status. RFS for LICAM positive and negative with NI, NO and Nx. D. Kaplan Meier LN status including ER/PR status. RFS for ER/PR positive and negative with NI, NO and Nx.

Abstract 295 Table 1

Cox regression analysis univariate and multivariate of disease specific survival (DSS)

Abstract 295 Table 2

Cox regression analysis univariate and multivariate of recurrence specific survival (RFS)

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.

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