Figure 4. Derived prognostic scores are not robust to multifocal prostate cancer with extreme grade differences.

(A) Derived prognostic scores (mxCCP, mxGPS, mxGC) from all profiled multifocal cases (MF2–8; MF1 in Figure 3) with extreme grade differences (i.e., at least 1 sample each from GG1 and ≥GG4 tumor foci). For each case, profiled samples are indicated by colored points overlying the overall cohort distribution, as in Figure 3C. (B) Histology and mxRNAseq support extreme multifocality in case MF3, which had a large pT3a GG5 index tumor focus (cyan) and a spatially distinct small GG1 focus (focus 5, green). Informative samples from the GG5 (orange) and GG1 (focus 5, green) foci are indicated (as well as a sampled area of normal prostate stroma in gray), with the chart showing sample name, profiled morphologic GG, and TP53 mutation/chromosome [chr] 9p deletion status, along with histopathology of the indicated samples (original magnification, ×4). The morphology and distinct TP53 p.C238Y/9p deletion status support clear multifocality, in addition to the unique T2:ERG isoform expression seen only in the GG1 focus (Figure 3A). (C) Derived prognostic scores are not robust to multifocal prostate cancer with extreme grade differences. Derived prognostic scores from all GG1 samples versus ≥GG4 tumor foci from the 8 multifocal cases with extreme grade group differences shown in Figure 3, A and C, are plotted (2-sample, unpaired 2-sided t test P values are shown).