Discrimination between low- and high-grade endometrial carcinomas (ECs) is clinically relevant but can be challenging for pathologists, with moderate interobserver agreement. Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is an oncofoetal protein that is associated with nonendometrioid endometrial carcinomas but has been limited studied in endometrioid carcinomas. The aim of this study is to investigate the diagnostic and prognostic value of IMP3 in the discrimination between low- and high-grade ECs and its added value to L1CAM. IMP3 and L1CAM expression was assessed in tumors from 378 patients treated for EC at 1 of 9 participating European Network for Individualised Treatment of Endometrial Cancer centers. IMP3 was expressed in 24.6% of the tumors. In general, IMP3 was more homogeneously expressed than L1CAM. IMP3 expression was significantly associated with advanced stage, nonendometrioid histology, grade 3 tumors, deep myometrial invasion, lymphovascular space invasion, distant recurrences, overall mortality, and disease-related mortality. Simultaneous absence of IMP3 and L1CAM expression showed the highest accuracy for identifying low-grade carcinomas (area under the curve 0.766), whereas simultaneous expression of IMP3 and L1CAM was strongly associated with high-grade carcinomas (odds ratio 19.7; 95% confidence interval 9.2-42.2). Even within endometrioid carcinomas, this combination remained superior to IMP3 and L1CAM alone (odds ratio 8.6; 95% confidence interval 3.4-21.9). In conclusion, IMP3 has good diagnostic value and together with L1CAM represents the optimal combination of diagnostic markers for discrimination between low- and high-grade ECs compared to IMP3 and L1CAM alone. Because of the homogenous expression of IMP3, this marker might be valuable in preoperative biopsies when compared to the more patchy L1CAM expression.

Biomedical Research Group in Gynaecology Vall Hebron Institute of Research Universitat Autònoma de Barcelona CIBERONC 08193 Barcelona Spain

Biomedical Research Group in Gynaecology Vall Hebron Institute of Research Universitat Autònoma de Barcelona CIBERONC 08193 Barcelona Spain; Gynecological Department Vall Hebron University Hospital CIBERONC 8035 Barcelona Spain

Department of Obstetrics and Gynaecology Canisius Wilhelmina Hospital 6500 GS Nijmegen the Netherlands

Department of Obstetrics and Gynaecology Haukeland University Hospital 5021 Bergen Norway; Centre for Cancer Biomarkers CCBIO Department of Clinical Science University of Bergen 5021 Bergen Norway

Department of Obstetrics and Gynaecology Hospital del Mar 8003 Barcelona Spain

Department of Obstetrics and Gynaecology Radboud University Medical Centre 6500HB Nijmegen the Netherlands

Department of Obstetrics and Gynaecology University Hospital Brno Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Department of Obstetrics and Gynaecology University Medical Centre Freiburg 79106 Freiburg Germany; German Cancer Consortium 69120 Heidelberg Germany

Department of Pathology and Molecular Genetics and Oncological Pathology Group Hospital Universitari Arnau de Vilanova University of Lleida IRBLLEIDA CIBERONC 25198 Lleida Spain

Department of Pathology Canisius Wilhelmina Hospital 6500 GS Nijmegen the Netherlands

Department of Pathology Ghent University Hospital 9000 Ghent Belgium

Department of Pathology Hospital del Mar 8003 Barcelona Spain

Department of Pathology Radboud University Medical Centre 6500HB Nijmegen the Netherlands

Department of Pathology Radboud University Medical Centre 6500HB Nijmegen the Netherlands; Radboud Institute for Molecular Life Sciences 6500HB Nijmegen the Netherlands

Department of Pathology University Hospital Brno Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Department of Pathology University of Turku 20500 Turku Finland

Division of Gynaecologic Oncology Department of Obstetrics and Gynaecology University Hospital Gasthuisberg 3000 Leuven Belgium

Division of Gynaecologic Oncology Department of Obstetrics and Gynaecology University Hospital Gasthuisberg 3000 Leuven Belgium; Department of Gynaecologic Oncology Centre Gynaecologic Oncology Amsterdam Netherlands Cancer Institute and Amsterdam University Medical Centres Academic Medical Centre 1105 AZ Amsterdam the Netherlands

Institute for Surgical Pathology Medical Centre University of Freiburg 79085 Freiburg Germany; Comprehensive Cancer Centre Freiburg Medical Centre University of Freiburg 79106 Freiburg Germany; Faculty of Medicine University of Freiburg 79085 Freiburg Germany

Obstetrics and Gynaecology Department Bichat Claude Bernard Hospital 75877 Paris France

Pathology Department Bichat Claude Bernard Hospital 75877 Paris France

Pathology Department Vall Hebron University Hospital 8035 Barcelona Spain

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