The nested variant of urothelial carcinoma (NVUC) is a rare bladder tumor that may possess a luminal molecular phenotype. We sought to determine whether a small immunohistochemical (IHC) panel using common surrogates for molecular phenotypes would reliably classify a cohort of pure NVUC cases.
IHC staining with a panel composed of markers for basal subtypes (CK5/6, CK14) and luminal subtypes (FOXA1, GATA3) was performed on pure small NVUC cases (n = 23) and 5 large NVUC cases (n = 5). Scoring of IHC stains was performed semiquantitatively. Individual cases were analyzed using previously reported IHC-based surrogates for molecular subtype.
The phenotype of NVUC was classified as luminal from 60.1% (FOXA1+/CK5/6-) to 100% (GATA3+/CK14-) of cases using composite phenotypes. No cases possessed a basal or squamous cell carcinoma-like phenotype. The majority of small NVUC cases (69.5%) showed subset CK5/6 expression distinctly localized to the basal layers of tumor cell nests. Intratumoral heterogeneity was also noted in CK5/6 (21.7% of small NVUC cases) but no other markers.
NVUC appears to express markers of both basal and luminal bladder tumors. Definitive gene expression profiling may be valuable to further characterize this unique histologic variant.

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