Nested Variant of Urothelial Carcinoma Is a Luminal Bladder Tumor With Distinct Coexpression of the Basal Marker Cytokeratin 5/6.

TitleNested Variant of Urothelial Carcinoma Is a Luminal Bladder Tumor With Distinct Coexpression of the Basal Marker Cytokeratin 5/6.
Publication TypeJournal Article
Year of Publication2021
AuthorsJohnson SM, Khararjian A, Legesse TB, Khani F, Robinson BD, Epstein JI, Wobker SE
JournalAm J Clin Pathol
Volume155
Issue4
Pagination588-596
Date Published2021 03 15
ISSN1943-7722
KeywordsAged, Biomarkers, Tumor, Carcinoma, Transitional Cell, Cohort Studies, Female, Humans, Keratin-5, Keratin-6, Male, Middle Aged, Retrospective Studies, Urinary Bladder Neoplasms
Abstract

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

DOI10.1093/ajcp/aqaa160
Alternate JournalAm J Clin Pathol
PubMed ID33118597
Related Faculty: 
Brian Robinson, M.D. Francesca Khani, M.D.

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