Prognostic stratification of muscle invasive urothelial carcinomas using limited immunohistochemical panel of Gata3 and cytokeratins 5/6, 14 and 20.

Genomic studies have delineated distinct molecular subgroups of urothelial carcinomas whose prognostic impact extends beyond traditional stage and grade groupings. The ' basal ' subgroup shows increased gene expression levels of KRT5 , KRT6 , and KRT14 and low expression levels of GATA binding protein 3, and is associated with an extremely poor outcome. Identification of this subset is necessary for improved patient management and research on targeted therapies. We aimed to assess the prognostic utility of immunohistochemistry (IHC) for basal markers: cytokeratin 5/6 (CK5/6) and 14 (CK14), and luminal markers: cytokeratin 20 (CK20) and Gata3 in muscle invasive urothelial carcinomas (MIBC). Study was of retrospective design (2014‐2017). All chemotherapy naïve patients of MIBC undergoing radical cystectomy were included. IHC was performed on formalin fixed paraffin-embedded whole tumor sections. Among 40 cases of MIBC included, 45% (18/40) were positive for one or both basal markers, 37.5% (15/40) were positive for one or both luminal markers, while 15% (6/40) were positive for both basal and luminal markers. One case did not express any of the four markers. MIBCs expressing only basal markers presented at an advanced stage with frequent squamous differentiation and showed a trend towards shorter overall survival. Gata3+ MIBCs showed the best outcome irrespective of expression of other markers, while CK14+/Gata3- MIBCs were associated with worst outcomes. Gata3-/CK14- MIBCs showed intermediate survival outcomes. CK5/6, CK20 and p53 expression did not significantly correlate with outcome. IHC for Gata-3 and CK14 stratified MIBC into distinct prognostic subsets. • Loss of Gata3 protein in MIBCs is an independent predictor of poor overall survival. • Cytokeratin-14 positive, Gata3 negative tumors associated with worst outcomes • Cytokeratin 5/6, cytokeratin 20 or p53 did not correlate with survival outcomes. • Combination of Gata3/cytokeratin-14 stratified MIBCs into three prognostic groups. [ABSTRACT FROM AUTHOR]