Kristin Astrid Berland Øystese1,2,3, Jens Petter Berg4,5, Kjersti Ringvoll Normann6,4,7, Manuela Zucknick8, Olivera Casar-Borota9,10,11, Jens Bollerslev6,4. 1. Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, P.b.4950 Nydalen, 0424, Oslo, Norway. k.a.b.oystese@medisin.uio.no. 2. Faculty of Medicine, University of Oslo, Oslo, Norway. k.a.b.oystese@medisin.uio.no. 3. Research Institute for Internal Medicine (IMF), OUS Rikshospitalet, Postboks 4950 Nydalen, 0424, Oslo, Norway. k.a.b.oystese@medisin.uio.no. 4. Faculty of Medicine, University of Oslo, Oslo, Norway. 5. Department of Medical Biochemistry, Oslo University Hospital, 0424, Oslo, Norway. 6. Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, P.b.4950 Nydalen, 0424, Oslo, Norway. 7. Research Institute for Internal Medicine (IMF), OUS Rikshospitalet, Postboks 4950 Nydalen, 0424, Oslo, Norway. 8. Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. 9. Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden. 10. Department of Clinical Pathology and Cytology, Uppsala University Hospital, Rudbeck Laboratory, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden. 11. Department of Pathology, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway.
Abstract
PURPOSE: Gonadotroph tumours are the most abundant of the clinically silent pituitary tumours. There is a lack of reliable prognostic markers predicting their clinical course. Our aim was to determine the level of E-cadherin and N-cadherin in a cohort of clinically silent gonadotroph pituitary tumours, and compare them to the rate of reintervention. METHODS: Tumour tissue from primary surgery was retrospectively investigated and compared with clinical data. Immunohistochemical (N = 105) and real time-qPCR (N = 85) analyses for the levels of N-cadherin and the extra- and intracellular domains of E-cadherin were performed. The immunoreactive scores (IRS) and mRNA relative quantity were compared to the rate of reintervention. RESULTS: The tumours presented a high IRS for N-cadherin (Median 12 (IQR 12-12)) and almost no immunoreactivity for the extracellular domain of E-cadherin (Median 0 (IQR 0-0)). The membranous staining for the intracellular domain of E-cadherin varied (Median 6 (IQR 4-6). Reduced membranous expression of the intracellular domain of E-cadherin was associated with nuclear presence of the same domain. Nuclear staining for the intracellular domain of E-cadherin was associated with a lower rate of reintervention (p = 0.01). CONCLUSION: We found that silent gonadotroph tumours presented high IRS for N-cadherin and low IRS for the extracellular domain of E-cadherin. A substantial proportion of the tumours presented nuclear staining for the intracellular domain of E-cadherin, accompanied by a reduced membranous expression of the intracellular domain of E-cadherin. Absence of nuclear staining for the intracellular domain of E-cadherin served as an independent predictor of reintervention.
PURPOSE: Gonadotroph tumours are the most abundant of the clinically silent pituitary tumours. There is a lack of reliable prognostic markers predicting their clinical course. Our aim was to determine the level of E-cadherin and N-cadherin in a cohort of clinically silent gonadotroph pituitary tumours, and compare them to the rate of reintervention. METHODS: Tumour tissue from primary surgery was retrospectively investigated and compared with clinical data. Immunohistochemical (N = 105) and real time-qPCR (N = 85) analyses for the levels of N-cadherin and the extra- and intracellular domains of E-cadherin were performed. The immunoreactive scores (IRS) and mRNA relative quantity were compared to the rate of reintervention. RESULTS: The tumours presented a high IRS for N-cadherin (Median 12 (IQR 12-12)) and almost no immunoreactivity for the extracellular domain of E-cadherin (Median 0 (IQR 0-0)). The membranous staining for the intracellular domain of E-cadherin varied (Median 6 (IQR 4-6). Reduced membranous expression of the intracellular domain of E-cadherin was associated with nuclear presence of the same domain. Nuclear staining for the intracellular domain of E-cadherin was associated with a lower rate of reintervention (p = 0.01). CONCLUSION: We found that silent gonadotroph tumours presented high IRS for N-cadherin and low IRS for the extracellular domain of E-cadherin. A substantial proportion of the tumours presented nuclear staining for the intracellular domain of E-cadherin, accompanied by a reduced membranous expression of the intracellular domain of E-cadherin. Absence of nuclear staining for the intracellular domain of E-cadherin served as an independent predictor of reintervention.
Authors: Anders J Kolnes; Kristin A B Øystese; Nicoleta C Olarescu; Geir Ringstad; Jon Berg-Johnsen; Olivera Casar-Borota; Jens Bollerslev; Anders P Jørgensen Journal: J Clin Endocrinol Metab Date: 2020-08-01 Impact factor: 5.958