Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.

Autor:	Uemura J; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan., Okano K; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan., Oshima M; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan., Suto H; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan., Ando Y; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan., Kumamoto K; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan., Kadota K; Department of Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan., Ichihara S; Department of Gastroenterological Surgery, Kagawa Prefectural Central Hospital, Kagawa, Japan., Kokudo Y; Department of Surgery, Kagawa Rosai Hospital, Kagawa, Japan., Maeba T; Department of Surgery, Japan Community Health Care Organization Ritsurin Hospital, Kagawa, Japan., Nanno Y; Division of Hepato-biliary-pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan., Toyama H; Division of Hepato-biliary-pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan., Takada Y; Department of Hepato-Biliary-Pancreatic and Brest Surgery, Ehime University Graduate School of Medicine, Ehime, Japan., Shimada M; Department of Digestive and Transplant Surgery, Tokushima University, Tokushima, Japan., Hanazaki K; Department of First Surgery, Kochi University School of Medicine, Kochi, Japan., Masaki T; Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan., Suzuki Y; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Jazyk:	angličtina
Zdroj:	Annals of surgery [Ann Surg] 2021 Dec 01; Vol. 274 (6), pp. e949-e956.
DOI:	10.1097/SLA.0000000000003624
Abstrakt:	Objective: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). Background: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. Methods: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. Results: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. Conclusions: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy. Competing Interests: The authors have no financial conflicts of interest related to this work. The authors report no conflicts of interest. (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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