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Added Value of Estrogen Receptor, Progesterone Receptor, and L1 Cell Adhesion Molecule Expression to Histology-Based Endometrial Carcinoma Recurrence Prediction Models: An ENITEC Collaboration Study
  1. Louis J.M. van der Putten, MD, PhD*,
  2. Nicole C.M. Visser, MD,
  3. Koen van de Vijver, MD, PhD,
  4. Maria Santacana, MD, PhD§,
  5. Peter Bronsert, MD, PhD,
  6. Johan Bulten, MD, PhD,
  7. Marc Hirschfeld, MD, PhD,#,
  8. Eva Colas, PhD**,
  9. Antonio Gil-Moreno, MD, PhD**,††,
  10. Angel Garcia, MD, PhD,,
  11. Gemma Mancebo, MD, PhD§§,
  12. Fransesc Alameda, MD, PhD∥∥,
  13. Jone Trovik, MD, PhD¶¶,
  14. Reidun K. Kopperud, PhD##,***,
  15. Jutta Huvila, MD†††,
  16. Stefanie Schrauwen, PhD‡‡‡,
  17. Martin Koskas, MD, PhD§,§§,
  18. Francine Walker, MD, PhD∥∥∥,
  19. Vit Weinberger, MD, PhD¶¶¶,
  20. Lubos Minar, MD, PhD¶¶¶,
  21. Eva Jandakova, MD, PhD###,
  22. Marc P.L.M. Snijders, MD, PhD****,
  23. Saskia van den Berg-van Erp, MD, PhD††††,
  24. Xavier Matias-Guiu, MD, PhD§,
  25. Helga B. Salvesen, MD, PhD¶¶,
  26. Henrica M.J. Werner, MD, PhD¶¶,
  27. Frederic Amant, MD, PhD‡‡‡,
  28. Leon F.A.G. Massuger, MD, PhD* and
  29. Johanna M.A. Pijnenborg, MD, PhD*
  1. * Departments of Obstetrics and Gynaecology, and
  2. Pathology, Radboud University Medical Center, Nijmegen;
  3. Department of Pathology, Anthoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands;
  4. § Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, CIBERONC, Lleida, Spain;
  5. Institute of Pathology,
  6. Department of Obstetrics and Gynecology, University Medical Center, Freiburg;
  7. # German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany;
  8. ** Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Autònoma de Barcelona, CIBERONC;
  9. †† Gynecological Department,
  10. ‡‡ Pathology Department, Vall Hebron University Hospital, CIBERONC; Departments of
  11. §§ Obstetrics and Gynecology, and
  12. ∥∥ Pathology, Hospital del Mar, Barcelona, Spain;
  13. ¶¶ Department of Obstetrics and Gynecology, Haukeland University Hospital;
  14. ## Department of Clinical Science,
  15. *** Center for Cancer Biomarkers, University of Bergen, Bergen, Norway;
  16. ††† Department of Pathology, University of Turku, Turku, Finland;
  17. ‡‡‡ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Leuven, Belgium; §§§Obstetrics and Gynecology Department,
  18. ∥∥∥ Pathology Department, Bichat-Claude Bernard Hospital, Paris, France;
  19. ¶¶¶ Department of Gynecology and Obstetrics,
  20. ### Institute of Pathology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Departments of
  21. **** Obstetrics and Gynaecology, and
  22. †††† Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
  1. Address correspondence and reprint requests to Louis van der Putten, MD, PhD, Department of Obstetrics and Gynaecology (791), Radboud University Medical Center, PO Box 9101, 6500HB, Nijmegen, the Netherlands. E-mail: Louis.vanderputten{at}


Objectives Endometrial carcinoma mortality is mainly caused by recurrent disease, and various immunohistochemical markers to predict recurrences have been studied. Loss of the estrogen receptor (ER) and progesterone receptor (PR) and the presence of the L1 cell adhesion molecule (L1CAM) are promising markers, but their combined value has not been studied.

Materials and Methods Expression of ER, PR, and L1CAM was immunohistochemically determined in 293 endometrial carcinomas from 11 collaborating European Network for Individualized Treatment of Endometrial Cancer centers. Estrogen receptor, PR, or L1CAM staining was considered positive or negative when expressed by greater than or equal to 10% or less than 10% of the tumor cells, respectively. The association between these markers and clinicopathological markers, and their combined value in predicting survival were calculated, both in the entire cohort and in a selected groups of stage I endometrioid and low-risk stage I endometrioid carcinomas.

Results Estrogen receptor and PR were negative in 19% and 28% of the cases, respectively, and L1CAM was positive in 18%. All 3 were associated with advanced stage, high-grade, nonendometrioid histology, lymphovascular space invasion (LVSI), and reduced disease-free survival. Only advanced stage, loss of PR, and LVSI were associated with reduced disease-free survival in multivariate analysis. A prognostic model including these 3 markers was superior to 1 including only the 3 immunohistochemical markers, which was superior to the traditional model. In both the stage I endometrioid and the low-risk stage I endometrioid groups, only loss of PR was associated with reduced disease-free survival.

Conclusions Loss of ER and PR, and the presence of L1CAM are associated with high risk characteristics, and loss of PR is the strongest predictor of recurrent disease. Although a combination of these 3 markers is slightly superior to the traditional histological markers, a prognostic model including stage, PR expression, and LVSI is the most promising model in the identification of high risk carcinomas. In the stage I endometrioid carcinomas, PR immunohistochemistry appears to be of additional value in predicting recurrences.

  • Endometrial carcinoma
  • Endometrioid
  • Nonendometrioid
  • Estrogen receptor
  • Progesteron receptor
  • L1CAM
  • Prognosis
  • Immunohistochemistry

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  • The authors declare no conflicts of interest.