|Title||Nested Variant of Urothelial Carcinoma Is a Luminal Bladder Tumor With Distinct Coexpression of the Basal Marker Cytokeratin 5/6.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Johnson SM, Khararjian A, Legesse TB, Khani F, Robinson BD, Epstein JI, Wobker SE|
|Journal||Am J Clin Pathol|
|Date Published||2021 03 15|
|Keywords||Aged, Biomarkers, Tumor, Carcinoma, Transitional Cell, Cohort Studies, Female, Humans, Keratin-5, Keratin-6, Male, Middle Aged, Retrospective Studies, Urinary Bladder Neoplasms|
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.
|Alternate Journal||Am J Clin Pathol|
Brian Robinson, M.D. Francesca Khani, M.D.