OBJECTIVE: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. METHODS: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. RESULTS: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. CONCLUSIONS: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

Amphia Hospital Department of Obstetrics and Gynecology Breda The Netherlands

Amphia Hospital Department of Pathology Breda The Netherlands

APHP Bichat Hospital Department of Obstetrics and Gynecology Paris France

Canisius Wilhelmina Hospital Department of Pathology Nijmegen The Netherlands

Catharina Hospital Department of Gynecology Eindhoven The Netherlands

CIBERONC IRBLleida University of Lleida Hospital Universitari Arnau de Vilanova Department of Pathology and Molecular Genetics and Research Laboratory Lleida Spain

CIBERONC Universitat Autònoma de Barcelona Vall d'Hebron Institute of Research Biomedical Research Group in Gynecology Barcelona Spain; CIBERONC Vall d'Hebron University Hospital Gynecological Department Barcelona Spain

Elisabeth TweeSteden Hospital Department of Gynecology Tilburg The Netherlands

Elisabeth TweeSteden Hospital Department of Pathology Tilburg The Netherlands

Elkerliek Hospital Department of Obstetrics and Gynecology Helmond The Netherlands

Eurofins PAMM Department of Pathology Eindhoven The Netherlands

Ghent University Hospital Department of Pathology Ghent Belgium

Hospital Universitari Arnau de Vilanova IRBLleida Lleida Institute for Biomedical Research Dr Pifarré Foundation Lleida Spain

Jeroen Bosch Hospital Department of Obstetrics and Gynecology 's Hertogenbosch The Netherlands

Jeroen Bosch Hospital Department of Pathology 's Hertogenbosch The Netherlands

KU Leuven Department of Oncology Leuven Belgium

Maastricht University Medical Center Department of Obstetrics and Gynecology Maastricht The Netherlands; GROW School for Oncology and Reproduction Maastricht The Netherlands

Maastricht University Medical Center Department of Pathology Maastricht The Netherlands

Maastricht University Medical Center Department of Pathology Maastricht The Netherlands; GROW School for Oncology and Reproduction Maastricht The Netherlands

Máxima Medical Center Veldhoven Department of Obstetrics and Gynecology Veldhoven The Netherlands

Medical Center University of Freiburg Department of Obstetrics and Gynecology Freiburg Germany

PSMAR Hospital del Mar Department of Obstetrics and Gynecology Barcelona Spain

Radboud University Medical Center Department of Obstetrics and Gynecology Nijmegen The Netherlands

Radboud University Medical Center Department of Pathology Nijmegen The Netherlands

University Hospital Brno and Masaryk University Department of Gynecology and Obstetrics Brno Czech Republic

University Hospital Brno and Masaryk University Department of Internal Medicine Hematology and Oncology Brno Czech Republic

University Hospital Brno and Masaryk University Department of Pathology Brno Czech Republic

University of Bergen Department of Clinical Science Center for Cancer Biomarkers Bergen Norway; Haukeland University Hospital Department of Obstetrics and Gynecology Bergen Norway

University of Bergen Department of Clinical Science Center for Cancer Biomarkers Bergen Norway; Haukeland University Hospital Department of Radiology Mohn Medical Imaging and Visualization Center Bergen Norway

University of Turku Department of Pathology Turku Finland

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