Stratification of urothelial bladder carcinoma depending on immunohistochemical expression of GATA3 and CK5/6

Abstract

ABSTRACT Bladder urothelial carcinoma (BUC) has two pathways with distinct molecular features and prognosis, non-muscle invasive (NMI) and muscle invasive (MI) tumors. The aim is to investigate the expression of GATA3 and CK5/6 in BUC with correlation to clinicopathologic parameters, including their impact on survival beside their potential use to stratify cases into prognostic subgroups. This study included 80 cases of BUC stained immunohistochemically by GATA3 and CK5/6. The cases were divided into four groups regarding expression status of both markers (luminal, basal, mixed, and null). GATA3 percentage of expression decreased in urothelial carcinoma with squamous differentiation, MI tumors, high-grade tumors, tumors with involved lymph nodes, presence of perineural invasion, presence of bilharziasis, presence of lympho-vascular invasion, and high mitotic count. CK5/6 positivity was higher in urothelial carcinoma cases with squamous differentiation, MI tumors, and presence of perineural invasion. Pure urothelial carcinoma and NMI were in favor of luminal group (GATA3 +ve/CK5/6 −ve). Univariate analysis showed that the presence of bilharziasis was associated with shorter PFS (p = .04). GATA3 and CK5/6 could be used for the stratification of urothelial bladder carcinoma into subtypes with different characteristics. Luminal bladder cancer represents the most common type (60%) that carries favorable features. Bilharziasis-associated urothelial carcinoma carries poor outcome manifested by short PFS.