Abstract
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.
Highlights
Urinary bladder cancer is among the top 10 most frequent cancers and one of the most common causes of cancer-related deaths in humans with an estimated 500,000 new cases and 200,000 deaths per year w orldwide[1,2]
GATA3 and CK5/6 immunopositivity was significantly associated with overall survival (OS) by log-rank analysis (Table 1)
Previous gene expression profiling has revealed that muscle-invasive bladder cancer (MIBC) can be subcategorized into at least three intrinsic subtypes including the luminal, basal, and double-negative subtypes[22]
Summary
Urinary bladder cancer is among the top 10 most frequent cancers and one of the most common causes of cancer-related deaths in humans with an estimated 500,000 new cases and 200,000 deaths per year w orldwide[1,2]. Studies of HER2/neu, E-cadherin, p53, and p16 expression in MIBC tumor tissue using immunohistochemistry (IHC) have been r eported[10]. None of these markers has been applied in clinical practice. Intrinsic subtypes of bladder cancer have demonstrated increased utility in predicting treatment outcomes, especially in patients with MIBC who undergo radical cystectomy followed by adjuvant c hemotherapy[18]. Previous studies have reported a correlation between mRNA expression profiles and IHC staining results in luminal (CK20 expression) and basal (CK5/6 expression) s ubtypes[11] and confirmed that GATA3 and CK5/6 expression by IHC may identify these two subtypes with greater than 90% accuracy according to a meta-analysis[19].
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