Representative examples of non-functional pancreatic neuroendocrine tumours (NF-PanNETs) that have been assessed by immunolabelling for ARX, PDX1, ATRX and DAXX, and telomere-specific fluorescence in situ hybridisation (FISH) for ALT. (A) NF-PanNET with positive expression for ARX (B) and negative expression for PDX1 (C), while both ATRX (D) and DAXX (E) exhibited preserved nuclear expression and an absence of alternative lengthening of telomeres (ALT) (F). (G) NF-PanNET with negative expression for ARX (H) and positive expression for PDX1 (I), while both ATRX (J) and DAXX (K) had preserved expression and an absence of ALT (L). (M) NF-PanNET with expression for both ARX (N) and PDX1 (O), but loss of nuclear ATRX (P) and preserved nuclear expression for DAXX (Q). the loss of ATRX expression correlated with the presence of large, ultrabright intranuclear foci by telomere-specific FISH, consistent with ALT (R). (S) NF-PanNET with positive ARX expression (T), negative PDX1 expression (U), preserved ATRX expression (V) and loss of DDAXX expression (W). Similar to loss of ATRX, DAXX-negative NF-PanNETs were associated with large, ultrabright telomere signals, consistent with ALT (X). ARX, aristaless-related homeobox gene; ATRX, alpha-thalassemia/mental retardation X-linked; DAXX, death domain-associated protein; PDX1, pancreatic and duodenal homeobox 1.