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

  1. aMajority of cases are pure ductal carcinoma in situ (24), three cases of ductal carcinoma in situ and adjacent invasive breast cancer