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Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology–Genomic Integration Analysis

Fig 2

Application of EDI to 1,026 breast tumors from the METABRIC study.

(A) The frequencies of EDI scores in breast tumors. (B) H&E staining, distribution of classified cells (green: cancer; blue: lymphocyte; red: stromal cells), and the heatmap of regional diversity scores for a tumor with the highest EDI score (EDI = 5). (C) Representative regions from each of the clusters k1–k5 are shown in a tumor with EDI = 5, with cluster k1 having the lowest diversity score and k5 the highest. By mapping regional clusters to the H&E image, we can begin to interpret these clusters with different cell diversity. We observed predominantly cancer cells in k1, increasingly more stromal cells and ductal in situ carcinoma cells (DCIS) in k2, and a vessel in k3. Cluster k4 features extensive stromal lymphocytes between ductal in situ carcinoma components, while k5 shows tumor-infiltrating lymphocytes (TIL) associated with invasive carcinoma cells.

Fig 2

doi: https://doi.org/10.1371/journal.pmed.1001961.g002