Expression of ATRX, DAXX, PDX1, ARX, and somatostatin receptors in pancreatic neuroendocrine tumors: a clinicopathological study.

BACKGROUND

Recent studies have identified ATRX/DAXX and PDX1/ARX as biomarkers defining novel pancreatic neuroendocrine tumor (PanNET) subtypes, while the clinical significance of somatostatin receptors (SSTRs) remains incompletely understood.

METHODS

We retrospectively analyzed 58 surgically resected primary PanNET samples and performed immunohistochemical evaluation of ATRX, DAXX, ARX/PDX1, and SSTR2a/5. The primary goal was to assess associations between biomarker expression and clinicopathological parameters. Secondary analyses explored relationships with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Quantitative expression scores were calculated, receiver operating characteristic (ROC) curve analysis was performed, and survival outcomes were assessed using Kaplan-Meier analysis.

RESULTS

The loss of DAXX or ATRX expression (86.3%) was more commonly observed in nonfunctional PanNETs cases compared to the functional PanNET group (13.7%) (p = 0.02). SSTR5 positive tumors were associated with longer median OS (73 vs. 7 months, p < 0.001) and RFS (36 vs. 6 months, p = 0.005). However, the difference in OS was not confirmed by Kaplan-Meier analysis (log-rank p = 0.078). In PanNETs ≥ 2 cm, a tumor size cutoff of 2.45 cm predicted ATRX/DAXX mutations with 96.9% sensitivity and 75% specificity (AUC 0.922, p = 0.007), in a cohort of 36 patients.

CONCLUSIONS

ATRX/DAXX loss was more prevalent in nonfunctional PanNETs (p = 0.02). Although SSTR5-positive tumors were associated with longer median OS, this difference was not confirmed by Kaplan-Meier analysis. Furthermore, tumor size demonstrates predictive value for ATRX/DAXX loss in PanNETs ≥2 cm, highlighting the relationship between tumor morphology and molecular alterations, however, this finding remains hypothesis-generating and requires further validation.