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- Title
Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations.
- Authors
Casar-Borota, Olivera; Boldt, Henning Bünsow; Engström, Britt Edén; Andersen, Marianne Skovsager; Baussart, Bertrand; Bengtsson, Daniel; Berinder, Katarina; Ekman, Bertil; Feldt-Rasmussen, Ulla; Höybye, Charlotte; Jørgensen, Jens Otto L.; Kolnes, Anders Jensen; Korbonits, Márta; Rasmussen, Åse Krogh; Lindsay, John R.; Loughrey, Paul Benjamin; Maiter, Dominique; Manojlovic-Gacic, Emilija; Pahnke, Jens; Poliani, Pietro Luigi
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs.<bold>Design: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
PITUITARY tumors; CARCINOMA; CUSHING'S syndrome
- Publication
Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 4, p1183
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgaa749