Fig. 2
Threshold effects in subtype classification lead to an overestimated prevalence of subtype shifts. a Barplot showing the proportions of each immunohistochemistry-subtype with discordant subtype classification. b Example of a quantitative analysis of subtype classification for a Basal/Squamous-like to Genomically Unstable discordant case. Red dots/lines show primary tumor values and blue dots/lines metastasis values. The pentagonal radar plot shows the paired samples’ correlation to the Lund2012 centroids. The triangular radar plot shows the immunohistochemistry classification scores: Scores on three panels result in classification as Basal/Squamous-like, Small-cell/neuroendocrine-like, or Mesenchymal-like when above cut-off (gray area). When below cut-off on all three axes, the Genomically Unstable–Urothelial-like axis determines subtype (dotted line indicates the cut-off value). c Selected immunostainings for the same case as in b. d Barplot showing the proportions of each immunohistochemistry-subtype with discordant subtype by centroid-based mRNA classification (n = 28), not validated by quantitative analysis or immunostaining. e Example of a quantitative analysis of subtype classification showing a “threshold effect”, i.e. a false discordant result. Data are shown as described in b. f Selected immunostainings for the same case as in e, showing no true subtype discordance. g Barplot showing the proportions of each immunohistochemistry-subtype with fully concordant subtype classification. h Example of a quantitative analysis of subtype classification for a concordant Urothelial-like tumor. i Selected immunostainings for the same case as in h. Tumor images are 300 × 300 μm. MIBC muscle-invasive bladder cancer, LNM lymph-node metastasis
