Real-World-Feasible Immunohistochemistry of ATRX, DAXX, and Menin Identifies a Subgroup of Non-Functioning Pancreatic Neuroendocrine Tumors with low Recurrence Risk to Guide De-Escalating Surveillance
In brief
No recurrences observed in menin-loss subgroup of resected non-functioning pancreatic NETs
In a retrospective series of 139 grade 1-2 non-functioning pancreatic neuroendocrine tumors, patients whose tumors showed isolated loss of Menin on immunohistochemistry (33 cases) experienced zero recurrences, compared with 12.5% in tumors with intact markers and 48% in ATRX/DAXX-loss tumors. The finding suggests Menin loss could identify a low-risk group for whom prolonged surveillance may be unnecessary, pending prospective validation.
- Journal
- Endocrine pathology (Q1)
- Published
- 29 August 2026
- Study design
- Cohort / observational study
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Anna Vera Ditte Verschuur, Wenzel Maximillian Hackeng, Jasvir Jairam, Busra Eldem, Jasmijn Sterre Westendorp, Menno Reginaldus Vriens, et al.
- PMID
- 42667492
- DOI
- 10.1007/s12022-026-09933-z
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 4 September 2026): IHC of ATRX/DAXX/Menin identifies low‑risk NF‑pNET subgroup
Abstract
Non-functioning pancreatic neuroendocrine tumors (NF-pNETs) show a variable prognosis. Despite 40-60% of patients remaining recurrence-free after surgery, guidelines recommend ≥ 10 years of follow-up. Recent studies identify prognostic subgroups based on ATRX, DAXX, and MEN1 mutations and chromosomal aneuploidy, highlighting a subgroup with favorable prognosis. We aimed to classify resected NF-pNETs into molecular subgroups using ATRX, DAXX, and Menin immunohistochemistry as surrogate markers for genomic status. To do so, we retrospectively collected resected primary sporadic grade 1 and 2 NF-pNETs without synchronous metastases from five international local pathology archives. ATRX, DAXX, and Menin immunohistochemistry was performed, and tumors were categorized into three groups: ATRX-DAXX-loss-group (ATRX or DAXX loss), isolated-Menin-loss-group (Menin loss without ATRX and DAXX loss), and unspecified-group (retained Menin, ATRX and DAXX). Kaplan-Meier analysis evaluated prognostic differences, and multivariable Cox regression assessed the added value of molecular subgroups beyond established prognostic factors. In total, 139 patients with grade 1 (64%) and 2 (36%) NF-pNETs were included. The median follow-up was 28 months (range 0-195) and recurrences occurred in 20% (28/139). No recurrences occurred in the isolated-Menin-loss-group (0/33), versus 12.5% (8/64) in the unspecified-group and 48% (20/42) in the ATRX-DAXX-loss-group. Kaplan-Meier analysis showed better recurrence-free interval in the isolated-Menin-loss-group than other subgroups (P < 0.001). In univariate analysis, the isolated-Menin-loss-group had a lower recurrence hazard (HR 0.03; 95%CI: 0.00-0.55; P = 0.018), than other subgroups, with little change in the hazard ratio after adjustment, but loss of significance. In conclusion, molecular subclassification by immunohistochemistry identifies NF-pNET patients with a low risk of recurrence and lays the groundwork for future prospective studies assessing genetics-based risk stratification as a tool for guiding clinical management.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.