BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

Center for Gynecologic Oncology Amsterdam Netherlands Cancer Institute 1066 CX Amsterdam The Netherlands

DCDC Tx B 5 5263 EM Vught The Netherlands

Department of Gynaecology and Obstetrics Amsterdam University Medical Centers University of Amsterdam 1105 AZ Amsterdam The Netherlands

Department of Gynaecology Catharina Hospital 5623 EJ Eindhoven The Netherlands

Department of Gynaecology Rijnstate Hospital 6815 AD Arnhem The Netherlands

Department of Gynecologic Oncology Erasmus MC Cancer Institute Erasmus Medical Center Rotterdam 3015 GD Rotterdam The Netherlands

Department of Gynecology and Obstetrics Haukeland University Hospital 5009 Bergen Norway

Department of Medical Oncology University Medical Center Utrecht 3584 CX Utrecht The Netherlands

Department of Obstetrics and Gynaecology Canisius Wilhelmina Hospital 6532 SZ Nijmegen The Netherlands

Department of Obstetrics and Gynaecology Radboud University Medical Centre 6525 GA Nijmegen The Netherlands

Department of Obstetrics and Gynecology Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Obstetrics and Gynecology Maastricht University Medical Center 6229 HX Maastricht The Netherlands

Department of Obstetrics and Gynecology University Hospital Brno 625 00 Brno Czech Republic

Department of Obstetrics and Gynecology University Medical Center Groningen 9713 GZ Groningen The Netherlands

Department of Pathology Radboud University Medical Center 6525 GA Nijmegen The Netherlands

Division of Medicine Department of Gynecological Oncology Oslo University Hospital 0424 Oslo Norway

Division of Obstetrics and Gynecology A Nocivelli Institute for Molecular Medicine ASST Spedali Civili di Brescia 25123 Brescia Italy

Faculty of Medicine Institute of Clinical Medicine University of Oslo 0372 Oslo Norway

GROW School of Oncology and Developmental Biology Maastricht University Medical Center 6229 ER Maastricht The Netherlands

InnoSIGN 5656 AE Eindhoven The Netherlands

Sultan Qaboos Comprehensive Cancer Center Muscat P O Box 566 PC 123 Oman

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