Fig. 1: Genetic, transcriptional, and protein alterations of the ERBB pathway in urothelial and squamous bladder cancer.

a Heatmap of mRNA expression of the ERBB receptor family for the BLCA TCGA data set. Samples are annotated with subtype cluster (red = Sq-BLCA, n = 85; blue = basal BLCA, n = 21; and green = luminal BLCA, n = 280), gender, stage, grade as well as mutational status and CNVs for EGFR and ERBB2–4. b Immunohistochemical EGFR (i and ii) and ERBB2/HER2 (iii and iv) protein expression of representative tumor tissues evaluated as intensity 0 and 3, respectively. Black scale bar: 100 µM. c Graph shows the frequency of EGFR protein intensity for Sq-BLCA samples (all; n = 116) and for subclasses mixed (MIX; n = 45) and pure SCC (SCC; n = 71). d Comparison of immunohistochemical results for EGFR protein expression between Sq-BLCA and urothelial carcinomas (muscle-invasive bladder cancer, MIBC) (Sq-BLCA n = 116, MIBC n = 63). e Graph illustrating the frequency of ERBB2/HER2 protein intensity for all Sq-BLCA (n = 117) and for subclasses mixed (MIX; n = 46) and pure SCC (SCC; n = 71). f Comparison of immunohistochemical results for ERBB2 protein expression between squamous-differentiated bladder tumors and MIBC (Sq-BLCA n = 117, MIBC n = 63). g Oncoprint graph highlighting mutations of genes involved in the ERBB signaling pathway (RAS genes, EGFR). FGFR3, and TP53 mutation analysis served as control (for detailed information on identified mutations see Supplementary Table 2); ***p < 0.001 (Mann–Whitney U test).