Casar-Borota, Olivera (54411899300)Olivera (54411899300)Casar-BorotaBoldt, Henninǵbünsow (7004515504)Henninǵbünsow (7004515504)BoldtEngström, Brittédén (7005863207)Brittédén (7005863207)EngströmAndersen, Marianne Skovsager (7403194727)Marianne Skovsager (7403194727)AndersenBaussart, Bertrand (8602898900)Bertrand (8602898900)BaussartBengtsson, Daniel (53879501800)Daniel (53879501800)BengtssonBerinder, Katarina (8853516100)Katarina (8853516100)BerinderEkman, Bertil (7003927285)Bertil (7003927285)EkmanFeldt-Rasmussen, Ulla (7005437081)Ulla (7005437081)Feldt-RasmussenHöybye, Charlotte (6602173681)Charlotte (6602173681)HöybyeJørgensen, Jens Otto L (8081653500)Jens Otto L (8081653500)JørgensenKolnes, Anders Jensen (36195381700)Anders Jensen (36195381700)KolnesKorbonits, Márta (7004190977)Márta (7004190977)KorbonitsRasmussen, Åse Krogh (7102424093)Åse Krogh (7102424093)RasmussenLindsay, John R (7201433530)John R (7201433530)LindsayLoughrey, Paul Benjamin (56993777000)Paul Benjamin (56993777000)LoughreyMaiter, Dominique (7005343694)Dominique (7005343694)MaiterManojlovic-Gacic, Emilija (36439877900)Emilija (36439877900)Manojlovic-GacicPahnke, Jens (16417489700)Jens (16417489700)PahnkePoliani, Pietro Luigi (57200074358)Pietro Luigi (57200074358)PolianiPopovic, Vera (35451450900)Vera (35451450900)PopovicRagnarsson, Oskar (54884610400)Oskar (54884610400)RagnarssonSchalin-Jäntti, Camilla (6701824881)Camilla (6701824881)Schalin-JänttiScheie, David (6507605065)David (6507605065)ScheieTóth, Miklós (57213773980)Miklós (57213773980)TóthVilla, Chiara (35424878200)Chiara (35424878200)VillaWirenfeldt, Martin (9042678300)Martin (9042678300)WirenfeldtKunicki, Jacek (7005533934)Jacek (7005533934)KunickiBurman, Pia (7004519451)Pia (7004519451)Burman2025-06-122025-06-122021https://doi.org/10.1210/clinem/dgaa749https://www.scopus.com/inward/record.uri?eid=2-s2.0-85100467499&doi=10.1210%2fclinem%2fdgaa749&partnerID=40&md5=a6d9affe59934b9d69ee3e13e15a82bfhttps://remedy.med.bg.ac.rs/handle/123456789/4282Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors. © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.aggressive PitNETsATRX (alpha thalassemia/mental retardation syndrome X-linked)Cushing's diseasepituitary adenomapituitary carcinoma