Expression profiling of 29 samples of microdissected HRS cells. (A) Unsupervised hierarchical cluster of 29 gene expression profiles is shown using the 200 genes with the highest variance. Red represents relative overexpression; and green, relative underexpression. Patient clusters, histologic subtype, EBV positivity of HRS cells by for EBV-encoded small RNA in situ hybridization, and sample type are shown. The average fold changes of genes representative of the 3 main signatures are shown in the bar plots. Representative immunohistochemistry images are depicted demonstrating cytoplasmic positivity of GrB (black arrows) and RANK in HRS cells. (B) Unsupervised hierarchical clustering of the cohort using the 200 most differentially expressed genes between primary treatment failure and success. Treatment outcome, histologic subtype, EBV positivity of HRS cells by for EBV-encoded small RNA in situ hybridization, and sample type are shown. Cases cluster according to the outcome groups (2 main clusters). Differentially expressed genes are given in the supplementary data (comparison gene lists).