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Activation of extracellular regulated kinases (ERK1/2) predicts poor prognosis in urothelial bladder carcinoma and is not associated with B‐Raf gene mutations

Aim: The analysis of the presence of B‐Raf gene mutations in relation to ERK1/2 activation in bladder urothelial carcinoma (UC), in order to determine their potential role in tumour aggressiveness and patients' survival. Methods: Polymerase chain reaction‐single strand confirmation polymorphism (PCR‐SSCP) and sequencing analysis were used for B‐Raf gene mutation detection. pERK1/2 and FGFR3 expression were examined by immunohistochemistry in 152 and 116 primary UCs, respectively. Results: None of the cases displayed mutations in exon 15 of B‐Raf gene. Nuclear or cytoplasmic pERK immunoreactivity was displayed in 99.3% and 96.7% of cases, respectively. pERK nuclear expression increased with histological grade and with T‐category. Nuclear and cytoplasmic pERK expression was unrelated to FGFR3 expression. In univariate survival analysis of muscle‐invasive carcinomas, advanced T‐category and higher pERK nuclear expression (p = 0.018) adversely affected survival. However, multivariate analysis in non‐invasive as well as in muscle‐invasive carcinomas selected only T‐category as a significant prognosticator. Conclusions: Our findings suggest that elevated pERK expression occurs in UCs in the absence of B‐Raf mutations and is not correlated with FGFR3 over‐expression. Moreover, it implicates ERK activation in the acquisition of a more aggressive phenotype. However, the assessment of pERK1/2 expression does not seem to add to the prognostic information provided by classical prognosticators.