S W Vrede1, W J van Weelden2, N C M Visser3, J Bulten4, L J M van der Putten2, K van de Vijver5, M Santacana6, E Colas7, A Gil-Moreno8, C P Moiola7, G Mancebo9, C Krakstad10, J Trovik11, I S Haldorsen12, J Huvila13, M Koskas14, V Weinberger15, M Bednarikova16, J Hausnerova17, A A van der Wurff18, X Matias-Guiu6, F Amant19, M P L M Snijders20, H V N Küsters-Vandevelde21, C Reijnen22, J M A Pijnenborg2. 1. Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, the Netherlands; Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. Electronic address: stephanie.vrede@radboudumc.nl. 2. Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, the Netherlands. 3. Department of Pathology, Stichting PAMM, Eindhoven, the Netherlands; Department of Pathology, Radboud university medical center, Nijmegen, the Netherlands. 4. Department of Pathology, Radboud university medical center, Nijmegen, the Netherlands. 5. Department of Pathology, Ghent University Hospital, Cancer Research Institute Ghent (CRIG), Ghent, Belgium. 6. Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, CIBERONC, Lleida, Spain. 7. Biomedical Research Group in Gynaecology, Vall Hebron Institute of Research, Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain. 8. Gynecological Department, Vall Hebron University Hospital, CIBERONC, Barcelona, Spain; Pathology Department, Vall Hebron University Hospital, CIBERONC, Barcelona, Spain. 9. Department of Obstetrics and Gynaecology, Hospital del Mar, PSMAR, Barcelona, Spain. 10. Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway. 11. Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway. 12. Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway. 13. Department of Pathology, University of Turku, Turku, Finland. 14. Department of Obstetrics and Gynaecology Department, Bichat-Claude Bernard Hospital, Paris, France. 15. Department of Obstetrics and Gynaecology, University Hospital in Brno and Masaryk University, Brno, Czech Republic. 16. Department of Internal Medicine, Hematology and Oncology, University Hospital in Brno and Masaryk University, Brno, Czech Republic. 17. Department of Pathology, University Hospital in Brno and Masaryk University, Brno, Czech Republic. 18. Department of Pathology, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands. 19. Department of Oncology, KU Leuven, Leuven, Belgium; Department of Gynaecologic Oncology, Netherlands Cancer Institute and Amsterdam Medical Centers, Amsterdam, the Netherlands. 20. Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 21. Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 22. Department of Radiation Oncology, Radboud university medical center, Nijmegen, the Netherlands.
Abstract
OBJECTIVE: Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. METHODS: Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. RESULTS: A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the 'high and advanced/metastatic' risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO 'high and advanced/metastatic' were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. CONCLUSION: The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.
OBJECTIVE: Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. METHODS: Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. RESULTS: A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the 'high and advanced/metastatic' risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO 'high and advanced/metastatic' were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. CONCLUSION: The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.