Bernardo C, et al. - Through a cohort of 344 luminal tumors categorized as urothelial-like (Uro), with the subtypes UroA, UroAp, UroB, and UroC, or genomically unstable (GU) according to the LundTax system, researchers intended to explicate that the UroAp, UroB, and UroC represent biologically progressed versions of the canonical UroA subtype, typically low-grade Ta tumors with characteristics matching the normal urothelium, and that the GU subtype is biologically distinct from the Uro class of tumors. Uro tumors form one, albeit heterogeneous, group identified by FGFR3, CCND1, and RB1 expression, although, low or absence of CDKN2A(p16) and ERBB2 expression was noted. In GU cases, the opposite expression pattern was perceived. Moreover, Uro tumors were differentiated from GU tumors by exhibiting a high RB1/p16 expression ratio. Class defining features were independent of pathological stage and growth pattern, and therefore, intrinsic. In Uro tumors, proliferation was restricted to a well-defined single layer of basal-like cells in UroA tumors, however, in the more progressed UroAp and UroC tumors, it occurred throughout the tumor parenchyma, independent of the basal layer. In GU, a comparable alteration in proliferation topology was not seen. Hence, it was concluded that, at the molecular pathology level, luminal urothelial carcinomas comprise of two major subtypes, the larger heterogenous Uro and the biologically different GU subtype.