Preoperative imaging markers and PDZ-binding kinase tissue expression predict low-risk disease in endometrial hyperplasias and low grade cancers
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Anna Berg1,2, Ankush Gulati3, Sigmund Ytre-Hauge3,4, Kristine E. Fasmer3, Karen K. Mauland1,2, Erling A. Hoivik1,2, Jenny A. Husby3,4, Ingvild L. Tangen1,2, Jone Trovik1,2, Mari K. Halle1,2, Ingunn Stefansson5,6, Lars A. Akslen5,6, Kathrine Woie2, Line Bjørge1,2, Helga B. Salvesen1,2, Øyvind O. Salvesen7, Henrica M.J. Werner1,2, Ingfrid S. Haldorsen3,4,* and Camilla Krakstad1,2,*
1Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway
2Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
3Department of Radiology, Haukeland University Hospital, Bergen, Norway
4Section of Radiology, Department of Clinical Medicine, University of Bergen, Norway
5Department of Pathology, Haukeland University Hospital, Bergen, Norway
6Department of Clinical Medicine, Centre for Cancer Biomarkers, Bergen, Norway
7Unit for Applied Clinical Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
*These authors have contributed equally to this work
Camilla Krakstad, email: [email protected]
Keywords: endometrial carcinoma, endometrial hyperplasia, PBK, MRI, FDG-PET/CT
Received: April 27, 2017 Accepted: June 19, 2017 Published: July 31, 2017
Purpose: Distinguishing complex atypical hyperplasia (CAH) from grade 1 endometrioid endometrial cancer (EECG1) preoperatively may be valuable in order to prevent surgical overtreatment, particularly in patients wishing preserved fertility or in patients carrying increased risk of perioperative complications.
Material and methods: Preoperative histological diagnosis and radiological findings were compared to final histological diagnosis in patients diagnosed with CAH and EECG1. Imaging characteristics at preoperative magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computer tomography (FDG-PET/CT) were compared with tumor DNA oligonucleotide microarray data, immunohistochemistry findings and clinicopathological annotations.
Results: MRI assessed tumor volume was higher in EECG1 than in CAH (p=0.004) whereas tumor apparent diffusion coefficient value was lower in EECG1 (p=0.005). EECG1 exhibited increased metabolism with higher maximum and mean standard uptake values (SUV) than CAH (p≤0.002). Unsupervised clustering of EECG1 and CAH revealed differentially expressed genes within the clusters, and identified PDZ-binding kinase (PBK) as a potential marker for selecting endometrial lesions with less aggressive biological behavior.
Conclusion: Both PBK expression and preoperative imaging yield promising biomarkers that may aid in the differentiation between EECG1 and CAH preoperatively, and these markers should be further explored in larger patient series.
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