DAXX/ATRX Loss and ALT as Prognostic Biomarkers in Pancreatic Neuroendocrine Tumors
This review summarizes the diagnostic and prognostic utility of DAXX and ATRX protein loss (detected by immunohistochemistry) and alternative lengthening of telomeres (detected by telomere FISH) in pancreatic neuroendocrine tumors. These markers help distinguish indolent from aggressive PanNETs, differentiate PanNETs from neuroendocrine carcinomas, and identify pancreatic origin in metastatic disease of unknown primary. The approach addresses a real clinical gap given that current grading systems do not reliably predict behavior in this heterogeneous tumor group.
The original study
The diagnostic and prognostic utility of incorporating DAXX, ATRX, and alternative lengthening of telomeres to the evaluation of pancreatic neuroendocrine tumors.
- Authors
- Heaphy CM, Singhi AD
- Journal
- Human pathology
- Type
- Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 35872157
Original 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.