Table 2 Overview of studies investigating the presence and/or potential significance of ductal carcinoma in situ-associated immune infiltrates
From: Tumor-infiltrating lymphocytes and ductal carcinoma in situ of the breast: friends or foes?
Year | Author | Number of patients | Cohort | Whole section vs tissue microarray | Immune cells | Immunohistochemical markers | Additional assays | Immune cells and histopathological features | Clinical outcome |
|---|---|---|---|---|---|---|---|---|---|
1997 | Lee | 41 | Ductal carcinoma in situ | Whole section | Cytotoxic T cells, regulatory T cells, B cells and tumor-associated macrophages | CD3, CD8, FOXP3, CD20, CD68 | Not applicable | Clustered immune pattern (high numbers of tumor-infiltrating lymphocytes and low numbers of tumor-associated macrophagess) is associated with high-grade ductal carcinoma in situ and HER2+ subtype | Not applicable |
2010 | Sharma | 285 | Ductal carcinoma in situ | Tissue microarray | Tumor-associated macrophages | CD138, CD163, MMP11 | Gene-expression analysis | Macrophage response signature is associated with high grade, ER−/PR− ductal carcinoma in situ | Not applicable |
2015 | Knopfelmacher | 46 | Ductal carcinoma in situ | Whole section | Tumor infiltrating lymphocytes | Not applicable | Gene-expression analysis | High numbers of tumor-infiltrating lymphocytes is associated with a high oncotype DX ductal carcinoma in situ score | Not applicable |
2016 | Morita | 82 | Ductal carcinoma in situ | Whole section and Tissue microarray | Cytotoxic T cells | CD8 | Not applicable | High numbers of tumor-infiltrating lymphocytes is associated with high numbers of CD8+ T cells, high grade, presence of comedonecrosis, HER2+, triple negative subtype and spontaneous “healing” | Not applicable |
2016 | Pruneri | 1488 | Ductal carcinoma in situ | Whole section | Tumor infiltrating lymphocytes | Not applicable | Not applicable | High numbers of tumor-infiltrating lymphocytes is associated with high grade, presence of comedonecrosis and HER2+ subtype | Tumor infiltrating lymphocytes number is not associated with ipsilateral recurrence |
2016 | Thompson | 27 | Ductal carcinoma in situ with invasive breast cancera | Tissue microarray | T helper cells, cytotoxic T cells, regulatory T cells and B cells | CD3, CD4, CD8, FOXP3, CD20, PD-L1 | Not applicable | Not applicable | Tumor infiltrating lymphocytes number is not associated with ipsilateral recurrence |
2016 | Semeraro | 199 | Ductal carcinoma in situ | Not applicable | Cytotoxic T cells and regulatory T cells | CD8 and FOXP3 | Not applicable | High numbers of CD8+ and FOXP3+ cells and high ratio of CD8+/FOXP3+ is associated with large tumor cell diameter | Low numbers of CD8+ cells and low CD8+/FOXP3+ ratio was associated with ipsilateral recurrence |
2016 | Kim | 177 | Ductal carcinoma in situ | Whole section | Tumor infiltrating lymphocytes and tertiary lymphoid structures | Not applicable | not applicable | High numbers of tumor-infiltrating lymphocytes and tertiary lymphoid structuress is associated with HER2+ and triple negative ductal carcinoma in situ | Not applicable |
2017 | Miligy | 36 | Ductal carcinoma in situ | Whole section | B cells, plasma cells and tertiary lymphoid structures | CD20,CD19 and CD138 | not applicable | High numbers of B cells and tertiary lymphoid structuress is associated with larger tumor size, HER2+ and ER−/PR− ductal carcinoma in situ | High numbers of B cells are associated with shorter recurrence free survival |
2017 | Campbell | 117 | Ductal carcinoma in situ | Whole section | T helper cells, cytotoxic T cells, regulatory T cells, B cells and tumor-associated macrophages | CD4, CD8, FOXP3, CD20, CD68, CD115, HLA-DR,HLA-DP, HLA-DQ, MRC1 and PCNA | Not applicable | CD68+Mac387+ and CD115+ macrophages are associated with high VNPI, high grade, presence of comedonecrosis and ER−/PR− ductal carcinoma in situ CD8+ or HLADR+ cells are associated with low-grade ductal carcinoma in situ and absence of comedonecrosis | Low number of CD8+HLADR+ cells is associated with high risk of ipsilateral recurrence. High number of CD8+HLADR+ cells in combination with low numbers of CD8+HLADR- or CD115+ cells is associated with low risk of ipsilateral recurrence |
2017 | Hendry | 138 | Ductal carcinoma in situ | Tissue microarray | Tumor infiltrating lymphocytes | PD-L1 | Copy number variation and mutation analysis | High numbers of tumor-infiltrating lymphocytes and PD-L1+ cells is associated with high grade, HER2+ and ER− ductal carcinoma in situ high numbers of tumor-infiltrating lymphocytes is associated with the presence of comedonecrosis. The number of tumor-infiltrating lymphocytes is higher in cases with high chromosomal copy number variation and TP53 mutation compared to cases with low chromosomal copy number variation, PIK3CA and GATA3 mutation | Not applicable |