Impact of immunohistochemistry-based subtyping of GATA3, CK20, CK5/6, and CK14 expression on survival after radical cystectomy for muscle-invasive bladder cancer

Molecular subtyping of muscle-invasive bladder cancer (MIBC) predicts disease progression and treatment response. However, standard subtyping based on transcriptomic analysis is relatively expensive. This study tried to use immunohistochemistry (IHC) to subtype MIBC based on GATA3, CK20, CK5/6, and CK14 protein expression. The IHC-based subtypes in MIBC subtypes were classified as luminal (GATA3(+) CK5/6(-), 38.6%), basal (GATA3(-)CK5/6(+), 12.9%), mixed (GATA3(+) CK5/6(+), 37.9%), and double-negative (GATA3(-)CK5/6(-), 10.6%) in 132 MIBC patients. All individual markers and clinicopathological parameters were analyzed against treatment outcomes after radical cystectomy. The mean patient age was 65.6 years, and the male to female ratio was 6.8:1. Positive IHC expression of GATA3, CK20, CK5/6, and CK14 were 80.3%, 50.8%, 42.4%, and 28.0%, respectively. Only GATA3 and CK5/6 were significantly associated with survival outcome (p values=0.004 and 0.02). The mixed subtype was significantly better in 5-year OS at 42.8%, whereas the double-negative subtype had the worst prognosis (5-year OS 7.14%). The double-negative subtype had a hazard ratio of 3.29 (95% CI 1.71-6.32). Subtyping using GATA3 and CK5/6 was applicable in MIBCs, and patients with the double-negative subtype were at the highest risk and may require more intensive therapy.