title: Expression and clinical relevance of paired box protein 7 and sex determining region Y-box 2 in canine corticotroph pituitary adenomas.
abstract: Pituitary-dependent hypercortisolism is a common endocrinopathy in dogs, caused by an adrenocorticotrophic hormone secreting pituitary tumour of the anterior or intermediate lobe. The prognosis of intermediate lobe adenomas is worse than that of anterior lobe adenomas, indicating the possible usefulness of melanotropic markers as prognosticators. Another possible origin of pituitary adenomas is found in cancer stem cells. The aim of the present study was to investigate the expression of melanotroph specific transcription factor paired box protein 7 (Pax7) and stem cell marker and reprogramming factor sex determining region Y-box 2 (Sox2) and to relate their expression to clinical parameters. The mean ± SD of labelling index (LI) for Pax7 was 8.6% ± 21.7% in the adenomas; 1/6 controls had positive staining (LI, 15.2%). For Sox2, the LI in the adenomas was 16.9% ± 15.2% and 19.5% ± 11.6% in the controls. Pax7 expression was significantly higher in enlarged pituitaries, compared to non-enlarged pituitaries (P = 0.05), but Pax7 or Sox2 immunopositivity did not correlate to other clinical parameters such as histological diagnosis, survival time or disease-free interval. Gene expression of Pax7 target genes, such as proconvertase 2 (PC2), pro-opiomelanocortin (POMC), and dopamine D2 receptor (DRD2), was significantly lower in the adenoma samples compared to normal tissue, indicating that Pax7 signalling was not activated in adenomas. It was suggested that Pax7 and Sox2 remain interesting targets for molecular investigations into their role in pituitary tumorigenesis, but were unsuitable as clinical prognosticators in dogs.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands. Electronic address: s.j.vanrijn@uu.nl.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: van Rijn
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
authors.forename: Marianne G
authors.initials: MG
authors.lastname: Pouwer
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
authors.forename: Marianna A
authors.initials: MA
authors.lastname: Tryfonidou
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.514, 3508 TD Utrecht, The Netherlands.
authors.forename: Guy C M
authors.initials: GC
authors.lastname: Grinwis
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
authors.forename: Joanne E E
authors.initials: JE
authors.lastname: van der Bend
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
authors.forename: Pauline E P F
authors.initials: PE
authors.lastname: Beukers
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
authors.forename: Nadie
authors.initials: N
authors.lastname: Vastenhout
authors.affiliation: Molecular Genetics Research Unit, Institut de recherches cliniques de Montréal, 110 avenue des Pins Ouest, Montréal, Quebec H2W 1R7, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Drouin
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
authors.forename: Louis C
authors.initials: LC
authors.lastname: Penning
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
authors.forename: Björn P
authors.initials: BP
authors.lastname: Meij
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000662:veterinary*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism
chemical_list: D051763:PAX7 Transcription Factor; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone
keywords: Canine; Hypercortisolism; Paired box protein 7; Pituitary gland; Sex determining region Y-box 2