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  3. Non-functional Pancreatic Neuroendocrine Tumours: Atrx/daxx And Alternative Lengthening Of Telomeres (alt) Are Prognostically Independent From Arx/pdx1 Expression And Tumour Size.
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  3. Non-functional Pancreatic Neuroendocrine Tumours: Atrx/daxx And Alternative Lengthening Of Telomeres (alt) Are Prognostically Independent From Arx/pdx1 Expression And Tumour Size.

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Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are

Wenzel M Hackeng1, Lodewijk A A Brosens1, Joo Young Kim2

  • 1Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands singhiad@upmc.edu wenzelhackeng@gmail.com l.a.a.brosens@umcutrecht.nl heaphyc@bu.edu.

Gut
|April 14, 2021

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
neuroendocrine tumorspancreatic endocrine tumourpancreatic islet cellpancreatic pathologypancreatic surgery

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Alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) loss and alternative lengthening of telomeres (ALT) are key prognostic markers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). These biomarkers are valuable for predicting outcomes in small NF-PanNETs and identifying primary tumors of unknown origin.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Genetics

Background:

  • Non-functional pancreatic neuroendocrine tumours (NF-PanNETs) require reliable prognostic biomarkers.
  • Previous studies suggested aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), ATRX/DAXX, and alternative lengthening of telomeres (ALT) as potential markers.
  • Comprehensive evaluation, especially in small tumors (≤2.0 cm) and across different NET sites, was lacking.

Purpose of the Study:

  • To evaluate the prognostic significance of ARX/PDX1 and ATRX/DAXX expression, and ALT status in a large cohort of neuroendocrine tumours (NETs).
  • To assess the utility of these biomarkers in non-functional pancreatic neuroendocrine tumours (NF-PanNETs), including small ones.
  • To determine the specificity of these markers for pancreatic origin in NETs of unknown primary site.

Main Methods:

  • Immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT were performed.
  • An international cohort of 1322 NETs was analyzed, including primary NF-PanNETs, NF-PanNET metastases, and non-pancreatic NETs.
  • Clinicopathological features and relapse-free survival (RFS) were correlated with biomarker status.

Main Results:

  • ATRX/DAXX loss and ALT were significantly associated with adverse prognostic findings and increased metastasis/recurrence (p<0.001).
  • Five-year RFS rates were substantially lower for patients with ATRX/DAXX-negative (40%) and ALT-positive (42%) NF-PanNETs compared to wild-type (85-86%).
  • ATRX/DAXX and ALT status were independent prognostic factors for RFS, particularly in small NF-PanNETs (≤2.0 cm). ARX/PDX1 expression did not independently correlate with RFS.

Conclusions:

  • ATRX/DAXX and ALT are crucial for prognostic evaluation of NF-PanNETs, including small tumors.
  • These biomarkers demonstrate high specificity for pancreatic origin among NET metastases of unknown primary.
  • ARX/PDX1 expression is not an independent prognostic factor for RFS in NF-PanNETs.