EGFR expression in urothelial carcinoma of the upper urinary tract is associated with disease progression and metaplastic morphology

Abstract

EGFR represents a promising therapeutic target in urothelial cancer (UC). Our study aimed to investigate the clinicopathological significance of EGFR in upper urinary tract UC. EGFR was immunohistochemically assessed (EGFR pharmDX kit(TM)) in 268 consecutive tumours using a tissue microarray technique and correlated with other histopathological parameters as well as patient outcome. EGFR immunoreactivity was observed in 140/253 (55%) evaluable UCs and was associated with high tumour stage (47% pTa/pT1 vs 66% pT2-pT4; p=0.003) and high tumour grade (45% low grade vs 67% high grade; p<0.001). In addition, EGFR expression was associated with metaplastic squamous and/or glandular differentiation (p<0.001). EGFR staining intensity was 1+ in 49%, 2+ in 31%, and 3+ in 20% of cases. EGFR 3+ staining intensity was associated with the occurrence of metastatic disease by univariate analysis (p=0.016). Multivariate analysis, however, proved only pT stage >1 (p<0.001) and high tumour grade (p<0.001) to be independent predictors of patient outcome. In conclusion, EGFR was significantly associated with advanced disease and metaplastic squamous and/or glandular differentiation. Since UCs with metaplastic morphology have been shown to be more resistant to conventional radiotherapy or chemotherapy, the strikingly strong EGFR expression in these tumours may offer a new perspective for affected patients.