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      Reprint of: The Diagnostic and Prognostic Utility of Incorporating DAXX, ATRX, and Alternative Lengthening of Telomeres (ALT) to the Evaluation of Pancreatic Neuroendocrine Tumors (PanNETs).

      1 , 2
      Human pathology
      Elsevier BV
      FISH, Neoplasia, Pancreas, Prognosis, Telomere

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          Abstract

          Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and an ill-defined pathobiology. Although many PanNETs are indolent and remain stable for years, a subset may behave aggressively and metastasize widely. Thus, the increasing and frequent detection of PanNETs presents a treatment dilemma. Current prognostic systems are susceptible to interpretation errors, sampling issues, and do not accurately reflect the clinical behavior of these neoplasms. Hence, additional biomarkers are needed to improve the prognostic stratification of patients diagnosed with a PanNET. Recent studies have identified alterations in death domain-associated protein 6 (DAXX) and alpha-thalassemia/mental retardation X-linked (ATRX), as well as alternative lengthening of telomeres (ALT), as promising prognostic biomarkers. This review summarizes the identification, clinical utility, and specific nuances in testing for DAXX/ATRX by immunohistochemistry and ALT by telomere-specific fluorescence in situ hybridization in PanNETs. Furthermore, a discussion on diagnostic indications for DAXX, ATRX, and ALT status is provided to include the distinction between PanNETs and pancreatic neuroendocrine carcinomas (PanNECs), and determining pancreatic origin for metastatic neuroendocrine tumors in the setting of an unknown primary.

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          Author and article information

          Journal
          Hum Pathol
          Human pathology
          Elsevier BV
          1532-8392
          0046-8177
          Feb 2023
          : 132
          Affiliations
          [1 ] Department of Medicine, Boston University, School of Medicine, Boston, MA, 02118, USA.
          [2 ] Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA. Electronic address: singhiad@upmc.edu.
          Article
          NIHMS1903201 S0046-8177(23)00015-1
          10.1016/j.humpath.2023.01.004
          10259096
          36702689
          e45518a0-d847-419f-99af-3c088a95b0ba
          History

          Neoplasia,Telomere,FISH,Pancreas,Prognosis
          Neoplasia, Telomere, FISH, Pancreas, Prognosis

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