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Predicting recurrence in pancreatic neuroendocrine tumours: role of ARX and alternative lengthening of telomeres (ALT).
- Source :
- Histopathology; Oct2023, Vol. 83 Issue 4, p546-558, 13p
- Publication Year :
- 2023
-
Abstract
- Background: While many pancreatic neuroendocrine tumours (PanNET) show indolent behaviour, predicting the biological behaviour of small nonfunctional PanNETs remains a challenge. Nonfunctional PanNETs with an epigenome and transcriptome that resemble islet alpha cells (ARX‐positive) are more aggressive than neoplasms that resemble islet beta cells (PDX1‐positive). In this study, we explore the ability of immunohistochemistry for ARX and PDX1 and telomere‐specific fluorescence in situ hybridisation (FISH) for alternative lengthening of telomeres (ALT) to predict recurrence. Methods: Two hundred fifty‐six patients with PanNETs were identified, and immunohistochemistry for ARX and PDX1 was performed. Positive staining was defined as strong nuclear staining in >5% of tumour cells. FISH for ALT was performed in a subset of cases. Results: ARX reactivity correlated with worse disease‐free survival (DFS) (P = 0.011), while there was no correlation between PDX1 reactivity and DFS (P = 0.52). ALT‐positive tumours (n = 63, 31.8%) showed a significantly lower DFS (P < 0.0001) than ALT‐negative tumours (n = 135, 68.2%). ARX reactivity correlated with ALT positivity (P < 0.0001). Among nonfunctional tumours, recurrence was noted in 18.5% (30/162) of ARX‐positive tumours and 7.5% (5/67) of ARX‐negative tumours. Among WHO grade 1 and 2 PanNETs with ≤2 cm tumour size, 14% (6/43) of ARX‐positive tumours recurred compared to 0 of 33 ARX‐negative tumours and 33.3% (3/9) ALT‐positive tumours showed recurrence versus 4.4% (2/45) ALT‐negative tumours. Conclusion: Immunohistochemistry for ARX and ALT FISH status may aid in distinguishing biologically indolent cases from aggressive small low‐grade PanNETs, and help to identify patients who may preferentially benefit from surgical intervention. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03090167
- Volume :
- 83
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Histopathology
- Publication Type :
- Academic Journal
- Accession number :
- 171903176
- Full Text :
- https://doi.org/10.1111/his.14996