Background and aims The cell-surface carbohydrate Lewis^y antigen (blood group 8, BG8) has recently been investigated in bladder cancer, but its role in the differential diagnosis of flat urothelial lesions of the bladder has not yet been systematically evaluated.

Methods 30 carcinoma in situ (CIS) and 30 non-CIS conditions of the bladder mucosa (four dysplasia and 26 reactive atypia according to consensus diagnoses) were comparatively assessed in terms of their Lewis^y antigen staining profiles by two independent clinical pathologists.

Results Lewis^y antigen expression differed significantly (p<0.001) between CIS (full thickness expression throughout the entire urothelium including the basal cell layer) and non-CIS conditions (patchy discontinuous expression restricted to individual cells scattered singly throughout the urothelial mucosa). The four dysplastic study cases showed Lewis^y antigen expression more closely related to the staining profiles observed in most of the reactive urothelial atypia. κ statistics showed excellent inter-observer agreement between both raters in terms of Lewis^y antigen staining evaluation (κ=0.9, p<0.001).

Conclusions The data hint at the cell-surface carbohydrate Lewis^y antigen as a so far neglected diagnostically useful marker to aid in the histological classification of conventionally equivocal flat urothelial lesions of the bladder in contemporary surgical pathology practice.