Table 4.

Frequency of expression or alteration of select important biomarkers in the metastatic setting of urthelial cancer. Abbreviations: APOBEC: Apolipoprotein B mRNA Editing Catalytic Poly-peptide-like; Ephb2: Ephrin B2; Ephb4: Ephrin B4; FGFR: Fibroblast Growth Factor Receptor; HER2: Human Epidermal Growth Factor Receptor 2; HRR: Homologous recombination repair; MIBC: Muscle-invasive bladder cancer; MMR: Mismatch Repair; MSI-H: Microsatellite instability -High; MSS: Microsatellite stability; MTAP: Methylhyoadenosine phosphorylase; NMIBC: Non-muscle invasive bladder cancer; TCGA: The Cancer Genome Atlas; TLS: Tertiary Lymphoid Structures; TMB: Tumor Mutational Burden; UC: Urothelial Cancer; dMMR: deficient mismatch repair.

Biomarkers	Expression in UC as Clinical Interest	Alteration in UC as Clinical Interest	Details about Frequency of Expression or Alteration
Nectin-4	X		Frequently expressed in 83% [90]
Trop-2	X		Frequently expressed in ≤83% [91]
FGFR	X	X	FGFR3 most frequently expressed FGF receptor in normal urothelium [92]; FGFR1-4 alterations in 33% [12]
Ephb-2/ Ephb4	X		Extremely low Ephb2 expression (~nil) and high Ephb4 expression in 94% [93]
HRR genes (BRCA1, BRCA2, ATM, CDK12, etc.)		X	HRR mutations identified in 31.4% of a TCGA cohort (n = 822) and 34.1% of a retrospective single-center cohort (n = 343) [94]
HER2	X	X	Expression in 6–37% Alteration in 12% [95]
MTAP		X	Loss in 28% [96]
APOBEC		X	Mutation signature in 80% [97]
MSS/MMR		X	Prevalence of dMMR in 6% of UC and 2% in BC; Prevalence of MSI-H in 3% of UC and 1% in BC [98]
TMB		X	High TMB in 26% of Stage II-Stage IV BC, low TMB in 74% of cases [99]
TLS	X		~25% of NMIBC and ~75% of MIBC [100]