Abstract
Cytokeratin 5 is a marker of basal molecular subtypes of muscle‐invasive bladder cancer (MIBC), which correlates with worse overall survival compared to luminal subtypes. Our observations have not confirmed CK5 as a marker of high‐grade (HG) disease in Ta non‐muscle‐invasive bladder cancer (NMIBC). Therefore, to understand the basal‐luminal immunohistochemistry profile in Ta NMIBC, we performed immunohistochemistry for CK5, P40, P63 (basal), GATA3 and CK20 (luminal) and studied the correlation with HG and clinical outcome in 109 patients with Ta NMIBC. HG and low‐grade (LG) diseases were scored in each patient. Four different CK5 patterns were evaluated: absent (median 41.3%), normal (72.5%), rising (84.4%) and full thickness (23.9%). The median percentage of GATA3 was 100%. HG disease and CK5 expression and rising CK5 pattern had a significant inverse correlation, whereas HG disease and CK20 expression had a significant positive correlation. We also found a significant inverse correlation between CK5 expression and CK20 expression. Quantitative PCR confirmed that the presence of CK5 correlated with up‐regulation of CK5 RNA. None of the markers could differentiate patients with regard to clinical outcome. Our results suggest a role for CK5 and CK20 in differentiating between LG and HG disease in Ta NMIBC.
Highlights
Bladder cancer (BC) is the seventh most common cancer worldwide in men, with a yearly incidence of approximately 549 000 cases.[1]
Given the contradictory findings reported in the RNA and IHC studies between non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC), we studied the IHC of the basal and luminal markers in a large group of patients with Ta NMIBC for the first time.[15]
To fully assess the heterogeneity of Ta NMIBC, we used a granular methodology in which we scored the tumour grade as the percentage of HG and LG disease in each patient and addressed four specific patterns of CK5 expression in IHC
Summary
Bladder cancer (BC) is the seventh most common cancer worldwide in men, with a yearly incidence of approximately 549 000 cases.[1]. In contrast to the findings in MIBC, transcriptional analysis of NMIBC Ta and T1 disease identified a basal subtype with improved progression-free survival (PFS) compared to the luminal subtype.[13] Interestingly, this basal NMIBC subtype has increased RNA expression of CK5, whereas luminal NMIBC subtypes have higher RNA expression of CK20, a marker of apical umbrella cells.[13] The luminal marker GATA3 was expressed at even higher levels in the basal subtype in NMIBC than the other subtypes.[13] Interestingly, sub-classification of T1 NMIBC using the RNA expression of CK5 and CK20 can be used for the successful stratification of patients, demonstrating worse recurrence-free survival (RFS) and PFS in patients with high CK20 and low CK5 expression.[14]. We aimed to identify correlations between these CK5 IHC patterns and CK5 RNA expression, tumour grading (%), the other basal/luminal IHC markers and RFS
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