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Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma

Histopathology Nov 03, 2019

Weyerer V, Weisser R, Moskalev EA, et al. - Sixty nested variant of urothelial carcinoma (NVUC, one of the most prevalent rare variant of urothelial differentiation) cases were obtained from various departments and TERT promoter mutation analysis was done in all samples using SNaPshot analysis in order to characterize NVUC, in one of the biggest cohorts till date, at the molecular level. An immunohistochemical marker panel to describe the molecular subtype was applied. A mutation of the TERT promoter was harboured by 62.5% of NVUC cases. Moreover, among the most commonly mutated genes determined via NGS analysis were P53, JAK3 and CTNNB1. Subtyping showed that all NVUC express luminal markers like CD24, FOXA1, GATA3 and CK20. In conclusion, NVUC belong to the luminal molecular subtype. Further, a subset of NVUC appears to be identified via mutations of the Wnt and inflammatory pathways, comprising of JAK3 mutations, suggesting a distinct biological background, in comparison with conventional urothelial bladder cancer.
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