Fig. 3: Immune cell density in the periductal stroma is associated with clinicopathological characteristics of DCIS.

A Heatmap of log(1 + cells/mm²) stromal immune cell density of immune cell subsets related to outcome, grade, ER status, HER2 status, COX-2 expression and Ki67 in 141 DCIS patients. Stromal immune cell density does not cluster with case–control status. Higher stromal immune cell density clusters with higher grade, negative ER status, positive HER2 status, presence of periductal fibrosis and Ki67 ≥ 14%. Unsupervised cluster analysis was carried using Euclidean distance on the log-transformed cell densities with complete linkage. White rectangles: ER, HER2, COX-2, Ki67 not assessable (N/A). Grey rectangles: FoxP3⁺ T-cells and CD8⁺Ki67⁺ T-cells not assessable (N/A). B Combined beeswarm- and boxplots of stromal immune cell density. Higher stromal immune cell density is significantly associated with ER-negative status, HER2-positive status, presence of periductal fibrosis and Ki67 ≥ 14%. Higher grade is significantly associated with higher stromal density of lymphocytes, CD3⁺ T-cells, CD8⁺CD3⁺ T-cells, CD20⁺ B-cells and FoxP3⁺CD3⁺ regulatory T-cells (Kruskal–Wallis test). Significant associations are indicated as: *P < 0.05, **P < 0.01 and ***P < 0.001. The central line in boxes represent the median value, boundaries of boxes represent the interquartile range (IQR), and ends of whiskers represent values at 1.5x IQR. ^aoutcome, 0 = controls and 1 = cases, ^bhistologic grade was based on nuclear grade. ^cperiductal fibrosis, 0 = periductal absent, 1 = present. ^dER, 0 = negative, 1 = positive; ER was considered positive when ≥10% of the luminal epithelial cells showed nuclear staining of any intensity. ^eHER2, 0 = negative, 1 = positive. ^fKi67 expression in DCIS cells, 0 = <14%, 1 = ≥14%. ^gCOX-2, 0 = low expression in DCIS cells, 1 = high expression in DCIS cells.