The diagnostic and prognostic utility of incorporating DAXX, ATRX, and alternative lengthening of telomeres to the evaluation of pancreatic neuroendocrine tumors

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 dete...

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Bibliographic Details
Published in:Human pathology 2022-11, Vol.129, p.11-20
Main Authors: Heaphy, Christopher M, Singhi, Aatur D
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Biomarkers
Biomarkers, Tumor - genetics
Cancer
Co-Repressor Proteins - metabolism
Genes
Humans
In Situ Hybridization, Fluorescence
Metastasis
Molecular Chaperones - metabolism
Mutation
Neuroendocrine tumors
Neuroendocrine Tumors - diagnosis
Neuroendocrine Tumors - genetics
Neuroendocrine Tumors - pathology
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Pancreatic cancer
Pancreatic Neoplasms - diagnosis
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Patients
Peptides
Prognosis
Surveillance
Telomere - pathology
X-linked Nuclear Protein - genetics
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Summary: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.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2022.07.015