• Marie Colombe Agahozo, Mieke R van Bockstal, Floris H Groenendijk, Thierry P P van den Bosch, Pieter J Westenend, and van DeurzenCarolien H MCHMDepartment of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands..
• Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. m.agahozo@erasmusmc.nl.
• Mod. Pathol. 2020 Feb 1; 33 (2): 196-205.

AbstractDuctal carcinoma in situ of the breast includes several subtypes with a divergent biological behavior. Data regarding the composition of ductal carcinoma in situ-associated immune cells and their potential role in progression is limited. We studied ductal carcinoma in situ-associated immune response by characterizing immune cell subsets according to ductal carcinoma in situ subtypes. Ductal carcinoma in situ-associated tumor infiltrating lymphocyte (TIL) density was evaluated based on hematoxylin and eosin (H&E)-stained sections from 473 patients. Cases were subtyped based on ER, PR, and HER2. Patients were categorized as TIL-high or low. Ductal carcinoma in situ-associated immune cells of TIL-high cases were immunostained on whole slides with CD4, CD8, CD20, CD68, FOXP3, and PD-L1 (SP142 and SP263). In total, 131/473 patients (28.0%) were considered as TIL-high. The percentage of TIL-high cases was significantly higher in HER2+ and triple-negative ductal carcinoma in situ (P < 0.0001). Overall, no statistical difference in immune cell composition according to subtypes was found. However, individual subtype comparison showed that ER+ HER2+ cases had a significantly higher proportion of CD8+ T cells compared with triple-negative cases (P = 0.047). In TIL-high cases, PD-L1-SP142 expression on tumor cells was associated with subtype (P = 0.037); the lowest number of positive cases was observed in the HER2+ subtype (independent of ER). However, in TIL-high ductal carcinoma in situ, PD-L1 expression by both clones was limited. In conclusion, high numbers of TILs are predominantly observed in HER+ and triple negative ductal carcinoma in situ. The ER+ HER2+ subtype seems to attract a higher proportion of CD8+ T cells compared with the triple negative subtype. Among TIL-high cases, the HER2+ subgroup had the lowest PD-L1-SP142 expression on tumor cells. This suggests a more pronounced antitumor immunity in HER2+ ductal carcinoma in situ, which could play a role in its biological behavior.

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