Ductal carcinoma in situ of the breast: immune cell composition according to subtype

Mod Pathol. 2020 Feb;33(2):196-205. doi: 10.1038/s41379-019-0331-8. Epub 2019 Aug 2.

Abstract

Ductal 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / analysis
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Intraductal, Noninfiltrating / chemistry
  • Carcinoma, Intraductal, Noninfiltrating / immunology*
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Carcinoma, Intraductal, Noninfiltrating / therapy
  • Female
  • Humans
  • Immunophenotyping
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Phenotype
  • Prognosis
  • Receptor, ErbB-2 / analysis
  • Retrospective Studies
  • Triple Negative Breast Neoplasms / chemistry
  • Triple Negative Breast Neoplasms / immunology*
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / therapy

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2