PMID- 37169669 OWN - NLM STAT- MEDLINE DCOM- 20230605 LR - 20230605 IS - 1424-3911 (Electronic) IS - 1424-3903 (Linking) VI - 23 IP - 4 DP - 2023 Jun TI - Endoscopic ultrasound fine-needle biopsy to assess DAXX/ATRX expression and alternative lengthening of telomeres status in non-functional pancreatic neuroendocrine tumors. PG - 429-436 LID - S1424-3903(23)00139-4 [pii] LID - 10.1016/j.pan.2023.05.002 [doi] AB - BACKGROUND/OBJECTIVES: Death domain-associated protein (DAXX) and/or alpha-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes mutations and alternative lengthening of telomeres (ALT) activation are associated with more aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PanNETs). We aimed to evaluate the reliability of such markers on endoscopic-ultrasound fine-needle biopsy (EUS-FNB) specimens. METHODS: Patients who underwent EUS-FNB and subsequent surgical resection for PanNETs between January 2017 and December 2019 were retrospectively identified. Immunohistochemistry (IHC) to evaluate DAXX/ATRX expression and fluorescence in situ hybridization (FISH) for ALT status were performed. Primary outcome was the concordance rate of markers expression between EUS-FNB and surgical specimens. Secondary aims were association between markers and lesion aggressiveness, their diagnostic performance in predicting aggressiveness, and agreement of preoperative and post-surgical Ki67-based grading. RESULTS: Forty-one NF-PanNETs (mean diameter 36.1 +/- 26.5 mm) were included. Twenty-four showed features of lesion aggressiveness. Concordance of expressions of DAXX, ATRX, and ALT status between EUS-FNB and surgical specimens were 95.1% (kappa = 0.828; p < 0.001), 92.7% (kappa = 0.626; p < 0.001), and 100% (kappa = 1; p < 0.001), respectively. DAXX/ATRX loss and ALT-positivity were significantly (p < 0.05) associated with metastatic lymphnodes and lymphovascular invasion. The combination of all tumor markers (DAXX/ATRX loss + ALT-positivity + grade 2) reached an accuracy of 73.2% (95%CI 57.1-85.8) in identifying aggressive lesions. Pre- and post-operative ki-67-based grading was concordant in 80.5% of cases (k = 0.573; p < 0.001). CONCLUSION: DAXX/ATRX expression and ALT status can be accurately evaluated in a preoperative setting on EUS-FNB samples, potentially improving the identification of patients with increased risk and poorer prognosis. CI - Copyright (c) 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved. FAU - Mastrosimini, Maria Gaia AU - Mastrosimini MG AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. FAU - Manfrin, Erminia AU - Manfrin E AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. FAU - Remo, Andrea AU - Remo A AD - Department of Pathology, ULSS9 "Scaligera", Verona, Italy. FAU - De Bellis, Mario AU - De Bellis M AD - Department of Surgery, Division of General and HPB Surgery, School of Medicine, University of Verona, Verona, Italy. FAU - Parisi, Alice AU - Parisi A AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. FAU - Pedron, Serena AU - Pedron S AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. FAU - Luchini, Claudio AU - Luchini C AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. FAU - Brunelli, Matteo AU - Brunelli M AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. FAU - Ammendola, Serena AU - Ammendola S AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. FAU - Bernardoni, Laura AU - Bernardoni L AD - Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. FAU - Conti Bellocchi, Maria Cristina AU - Conti Bellocchi MC AD - Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. FAU - Gabbrielli, Armando AU - Gabbrielli A AD - Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. FAU - Facciorusso, Antonio AU - Facciorusso A AD - Department of Medical and Surgical Sciences, Section of Gastroenterology, University of Foggia, Foggia, Italy. FAU - Pea, Antonio AU - Pea A AD - General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. FAU - Landoni, Luca AU - Landoni L AD - General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. FAU - Scarpa, Aldo AU - Scarpa A AD - Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy; ARC-NET Applied Research on Cancer Centre, University of Verona, Verona, Italy. FAU - Crino, Stefano Francesco AU - Crino SF AD - Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. Electronic address: stefanocrino@hotmail.com. LA - eng PT - Journal Article DEP - 20230505 PL - Switzerland TA - Pancreatology JT - Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] JID - 100966936 RN - EC 3.6.4.12 (X-linked Nuclear Protein) RN - EC 3.6.4.12 (ATRX protein, human) RN - 0 (DAXX protein, human) RN - 0 (Molecular Chaperones) RN - 0 (Co-Repressor Proteins) SB - IM MH - Humans MH - X-linked Nuclear Protein/genetics/metabolism MH - *Neuroendocrine Tumors/diagnosis/genetics/surgery MH - Retrospective Studies MH - Biopsy, Fine-Needle MH - In Situ Hybridization, Fluorescence MH - *Intellectual Disability MH - *alpha-Thalassemia MH - Reproducibility of Results MH - *Pancreatic Neoplasms/diagnosis/genetics/surgery MH - Telomere/genetics/metabolism/pathology MH - Molecular Chaperones/genetics MH - Co-Repressor Proteins/genetics OTO - NOTNLM OT - ALT OT - FISH OT - Immunohistochemistry OT - Pancreatic cancer OT - Pancreatic tumor EDAT- 2023/05/12 01:07 MHDA- 2023/06/05 06:42 CRDT- 2023/05/11 22:01 PHST- 2022/09/25 00:00 [received] PHST- 2023/04/02 00:00 [revised] PHST- 2023/05/01 00:00 [accepted] PHST- 2023/06/05 06:42 [medline] PHST- 2023/05/12 01:07 [pubmed] PHST- 2023/05/11 22:01 [entrez] AID - S1424-3903(23)00139-4 [pii] AID - 10.1016/j.pan.2023.05.002 [doi] PST - ppublish SO - Pancreatology. 2023 Jun;23(4):429-436. doi: 10.1016/j.pan.2023.05.002. Epub 2023 May 5.