LGR5 as a diagnostic marker for dysplasia in serrated polyps.

Aims: WNT signalling pathway dysregulation is often a critical early component in colorectal neoplasia, particularly the chromosomal instability pathway. Using two WNT reporters, LGR5 and AXIN2, we sought to assess whether these polyps demonstrate predictable expression patterns and if these patterns show diagnostic value.

Methods: We evaluated 23 adenomas (TA), 23 sessile serrated lesions (SSLs), 14 SSL with dysplasia and 38 traditional serrated adenomas (TSA). Chromogenic in situ hybridisation stains (ISH) for LGR5 and AXIN2 were performed. Reactivity was defined as strong, intermediate or weak. Upper third crypt reactivity was defined as full-thickness staining. Accentuation within ectopic crypts (ECF) was recorded.

Results: TAs (91%) showed strong reactivity and full-thickness staining with LGR5. TSAs showed full-thickness and weak to intermediate LGR5 reactivity (79%) and ECF with LGR5 accentuation was exclusively seen in TSA. SSL showed weak LGR5 reactivity confined to the basal crypt region (100%). SSL with dysplasia also showed weak or intermediate (100%) LGR5 reactivity, but the reactivity pattern was full thickness (88%). AXIN2 expression parallels LGR5 expression (Pearson coefficient=0.63) regarding signal intensity for the examined polyp groups.

Conclusions: Qualitative and quantitative differences in AXIN2 and LGR5 expression assist in the diagnosis of SSL with dysplasia.