Publication details

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

Authors	PUTTEN Louis J. van der VISSER Nicole C. M. VIJVER Ko van de SANTACANA Maria BRONSERT Peter BULTEN Johan HIRSCHFELD Marc COLAS Eva GIL-MORENO Antonio GARCIA Angel MANCEBO Gemma ALAMEDA Fransesca TROVIK Jone KOPPERUD Reidun K. HUVILA Jutta SCHRAUWEN Stefanie KOSKAS Martin WALKER Francine WEINBERGER Vít MINÁŘ Luboš JANDÁKOVÁ Eva SNIJDERS Marc P. L. M. VAN DEN BERG-VAN ERP Sa MATIAS-GUIU Xavier SALVESEN Helga B. WERNER Henrica M. J. AMANT Frederic MASSUGER Leon F. A. G. PIJNENBORG Johanna M. A.
Year of publication	2018
Type	Article in Periodical
Magazine / Source	International Journal of Gynecological Cancer
MU Faculty or unit	Faculty of Medicine
Citation
Doi	http://dx.doi.org/10.1097/IGC.0000000000001187
Keywords	Endometrial carcinoma; Endometrioid; Nonendometrioid; Estrogen receptor; Progesteron receptor; L1CAM; Prognosis; Immunohistochemistry
Description	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.