Loss of progesterone receptor links to high proliferation and increases from primary to metastatic endometrial cancer lesions |
| |
| Affiliation: | 1. Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Norway;2. Department of Gynecology and Obstetrics, Haukeland University Hospital, Norway;3. Computational Biology Unit, University of Bergen, Bergen, Norway;4. Department of Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA;1. Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China;2. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210002, China;1. Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;2. Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;3. Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;4. Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;5. Electrical Engineering (ESAT-SISTA), KU Leuven, Herestraat 49, 3000 Leuven, Belgium;6. Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;7. General Medical Oncology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;8. Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;1. Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA;2. Wolfson Centre for Mathematical Biology, Mathematical Institute, Radcliffe Observatory Quarter, University of Oxford, Woodstock Road, Oxford OX2 6GG, UK;3. Mathematical Sciences, University of Gothenburg and Chalmers University of Technology, 412 96 Gothenburg, Sweden;1. Department of Gynaecology and Obstetrics, University Ulm, Prittwitzstraße 43, 89075 Ulm, Germany;2. Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 69, 55131 Mainz, Germany;3. Department of economics, Institute for medical biostistics, epidemiology and informatics, University medical centre, Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 69, Mainz, Germany;1. Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany;2. Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;3. Institute of Radiotherapy, University of Cologne, Cologne, Germany;1. INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France;2. Normandy University, Normandy, France;3. Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, Faculty of Sciences Dhar-El Mahraz, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco;4. Department of Pathology, University Hospital Hassan II, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco |
| |
| Abstract: | ObjectiveIn endometrial cancer loss of progesterone receptor (PR, gene name PGR) is associated with aggressive disease and altered response to hormonal treatment. The aim of this study was to investigate changes in PR expression level with disease progression, and explore whether differences in gene expression according to PR status can be linked to processes involved in cancer development elucidating new therapeutic opportunities.Methods686 primary endometrial cancers and 171 metastatic lesions were investigated for PR expression in relation to clinical and histopathological data. Protein levels were investigated by immunohistochemistry and reverse phase protein array, and mRNA levels by DNA oligonucleotide microarray.ResultsPR protein level was significantly associated with PGR mRNA expression (P < 0.001) and patient survival (P < 0.001). Loss of PR increased with disease progression, with 23% of the primary tumours and 76% of metastases demonstrating PR loss. Using a cell cycle progression signature score, PR loss was associated with increased proliferation for both oestrogen receptor (ER) positive and negative tumours. Through a Connectivity Map search, CDK inhibitors and other drugs with anti-proliferative effects were suggested in particular for treatment of patients with loss of PR.ConclusionLoss of PR in endometrial cancer is associated with increased proliferation, poor survival, and increases from primary to metastatic lesions. Based on expression profiles, CDK inhibitors may have activity in PR negative tumours, supporting further testing in clinical trials for patients with systemic endometrial cancer dependent on PR status. |
| |
| Keywords: | Endometrial cancer Progesterone receptor Survival CDK inhibitors |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
