Supplementary Figure 2 from Bladder Tumor Subtype Commitment Occurs in Carcinoma In Situ Driven by Key Signaling Pathways Including ECM Remodeling

(A) Unsupervised hierarchical clustering of tumor subtyping protein markers determined by semiquantitative immunohistochemistry (CK5, CK14, CD44, CK20, GATA3, FOXA1, UPKII) reveals a basal and luminal cluster. (B) HER2/neu protein expression (left panel) and ERBB2/CEN17-ratio in the WBHM samples. HER2/neu protein expression and its genetically detected ERBB2-gene locus amplification co-occur in CIS, pT1 carcinomas and MIBCs. (C) Distribution of "Normal-like", "Transforming-like" and "Invasive-like" cluster assignments in the WBHM scheme illustrates "Invasive-like" lesions surrounded by "Transforming-like" lesions. CIS = Carcinoma in situ; DYS = Dysplasia; UPUMP/HYP = urothelial proliferation of unknown malignant potential/ hyperplasia (abbreviated as "HYP" in graphs); IRS = Immunoreactive score; MIBC = Muscle-invasive bladder cancer; pT1 = Stroma invasive bladder cancer; U = Tumor associated urothelium.