Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast

Michael J. Campbell, Frederick Baehner, Tess O’Meara, Ekene Ojukwu, Booyeon Han, Rita Mukhtar, Vickram Tandon, Max Endicott, Zelos Zhu, Jasmine Wong, Gregor Krings, Alfred Au, Joe Gray, Laura Esserman

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Purpose: The recent increase in the incidence of ductal carcinoma in situ (DCIS) has sparked debate over the classification and treatment of this disease. Although DCIS is considered a precursor lesion to invasive breast cancer, some DCIS may have more or less risk than is realized. In this study, we characterized the immune microenvironment in DCIS to determine if immune infiltrates are predictive of recurrence. Methods: Fifty-two cases of high-grade DCIS (HG-DCIS), enriched for large lesions and a history of recurrence, were age matched with 65 cases of non-high-grade DCIS (nHG-DCIS). Immune infiltrates were characterized by single- or dual-color staining of FFPE sections for the following antigens: CD4, CD8, CD20, FoxP3, CD68, CD115, Mac387, MRC1, HLA-DR, and PCNA. Nuance multispectral imaging software was used for image acquisition. Protocols for automated image analysis were developed using CellProfiler. Immune cell populations associated with risk of recurrence were identified using classification and regression tree analysis. Results: HG-DCIS had significantly higher percentages of FoxP3+ cells, CD68+ and CD68+PCNA+ macrophages, HLA-DR+ cells, CD4+ T cells, CD20+ B cells, and total tumor infiltrating lymphocytes compared to nHG-DCIS. A classification tree, generated from 16 immune cell populations and 8 clinical parameters, identified three immune cell populations associated with risk of recurrence: CD8+HLADR+ T cells, CD8+HLADR T cells, and CD115+ cells. Conclusion: These findings suggest that the tumor immune microenvironment is an important factor in identifying DCIS cases with the highest risk for recurrence and that manipulating the immune microenvironment may be an efficacious strategy to alter or prevent disease progression.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Oct 26 2016

Fingerprint

Carcinoma, Intraductal, Noninfiltrating
Breast
Recurrence
Proliferating Cell Nuclear Antigen
HLA-DR Antigens
T-Lymphocytes
Population
CD8 Antigens
Tumor-Infiltrating Lymphocytes
CD4 Antigens
Tumor Microenvironment
Disease Progression
B-Lymphocytes
Software
Color
Macrophages
Regression Analysis
Staining and Labeling
Breast Neoplasms
Incidence

Keywords

  • Breast
  • DCIS
  • Immune microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Campbell, M. J., Baehner, F., O’Meara, T., Ojukwu, E., Han, B., Mukhtar, R., ... Esserman, L. (Accepted/In press). Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast. Breast Cancer Research and Treatment, 1-12. https://doi.org/10.1007/s10549-016-4036-0

Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast. / Campbell, Michael J.; Baehner, Frederick; O’Meara, Tess; Ojukwu, Ekene; Han, Booyeon; Mukhtar, Rita; Tandon, Vickram; Endicott, Max; Zhu, Zelos; Wong, Jasmine; Krings, Gregor; Au, Alfred; Gray, Joe; Esserman, Laura.

In: Breast Cancer Research and Treatment, 26.10.2016, p. 1-12.

Research output: Contribution to journalArticle

Campbell, MJ, Baehner, F, O’Meara, T, Ojukwu, E, Han, B, Mukhtar, R, Tandon, V, Endicott, M, Zhu, Z, Wong, J, Krings, G, Au, A, Gray, J & Esserman, L 2016, 'Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast', Breast Cancer Research and Treatment, pp. 1-12. https://doi.org/10.1007/s10549-016-4036-0
Campbell, Michael J. ; Baehner, Frederick ; O’Meara, Tess ; Ojukwu, Ekene ; Han, Booyeon ; Mukhtar, Rita ; Tandon, Vickram ; Endicott, Max ; Zhu, Zelos ; Wong, Jasmine ; Krings, Gregor ; Au, Alfred ; Gray, Joe ; Esserman, Laura. / Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast. In: Breast Cancer Research and Treatment. 2016 ; pp. 1-12.
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abstract = "Purpose: The recent increase in the incidence of ductal carcinoma in situ (DCIS) has sparked debate over the classification and treatment of this disease. Although DCIS is considered a precursor lesion to invasive breast cancer, some DCIS may have more or less risk than is realized. In this study, we characterized the immune microenvironment in DCIS to determine if immune infiltrates are predictive of recurrence. Methods: Fifty-two cases of high-grade DCIS (HG-DCIS), enriched for large lesions and a history of recurrence, were age matched with 65 cases of non-high-grade DCIS (nHG-DCIS). Immune infiltrates were characterized by single- or dual-color staining of FFPE sections for the following antigens: CD4, CD8, CD20, FoxP3, CD68, CD115, Mac387, MRC1, HLA-DR, and PCNA. Nuance multispectral imaging software was used for image acquisition. Protocols for automated image analysis were developed using CellProfiler. Immune cell populations associated with risk of recurrence were identified using classification and regression tree analysis. Results: HG-DCIS had significantly higher percentages of FoxP3+ cells, CD68+ and CD68+PCNA+ macrophages, HLA-DR+ cells, CD4+ T cells, CD20+ B cells, and total tumor infiltrating lymphocytes compared to nHG-DCIS. A classification tree, generated from 16 immune cell populations and 8 clinical parameters, identified three immune cell populations associated with risk of recurrence: CD8+HLADR+ T cells, CD8+HLADR− T cells, and CD115+ cells. Conclusion: These findings suggest that the tumor immune microenvironment is an important factor in identifying DCIS cases with the highest risk for recurrence and that manipulating the immune microenvironment may be an efficacious strategy to alter or prevent disease progression.",
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AU - Han, Booyeon

AU - Mukhtar, Rita

AU - Tandon, Vickram

AU - Endicott, Max

AU - Zhu, Zelos

AU - Wong, Jasmine

AU - Krings, Gregor

AU - Au, Alfred

AU - Gray, Joe

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N2 - Purpose: The recent increase in the incidence of ductal carcinoma in situ (DCIS) has sparked debate over the classification and treatment of this disease. Although DCIS is considered a precursor lesion to invasive breast cancer, some DCIS may have more or less risk than is realized. In this study, we characterized the immune microenvironment in DCIS to determine if immune infiltrates are predictive of recurrence. Methods: Fifty-two cases of high-grade DCIS (HG-DCIS), enriched for large lesions and a history of recurrence, were age matched with 65 cases of non-high-grade DCIS (nHG-DCIS). Immune infiltrates were characterized by single- or dual-color staining of FFPE sections for the following antigens: CD4, CD8, CD20, FoxP3, CD68, CD115, Mac387, MRC1, HLA-DR, and PCNA. Nuance multispectral imaging software was used for image acquisition. Protocols for automated image analysis were developed using CellProfiler. Immune cell populations associated with risk of recurrence were identified using classification and regression tree analysis. Results: HG-DCIS had significantly higher percentages of FoxP3+ cells, CD68+ and CD68+PCNA+ macrophages, HLA-DR+ cells, CD4+ T cells, CD20+ B cells, and total tumor infiltrating lymphocytes compared to nHG-DCIS. A classification tree, generated from 16 immune cell populations and 8 clinical parameters, identified three immune cell populations associated with risk of recurrence: CD8+HLADR+ T cells, CD8+HLADR− T cells, and CD115+ cells. Conclusion: These findings suggest that the tumor immune microenvironment is an important factor in identifying DCIS cases with the highest risk for recurrence and that manipulating the immune microenvironment may be an efficacious strategy to alter or prevent disease progression.

AB - Purpose: The recent increase in the incidence of ductal carcinoma in situ (DCIS) has sparked debate over the classification and treatment of this disease. Although DCIS is considered a precursor lesion to invasive breast cancer, some DCIS may have more or less risk than is realized. In this study, we characterized the immune microenvironment in DCIS to determine if immune infiltrates are predictive of recurrence. Methods: Fifty-two cases of high-grade DCIS (HG-DCIS), enriched for large lesions and a history of recurrence, were age matched with 65 cases of non-high-grade DCIS (nHG-DCIS). Immune infiltrates were characterized by single- or dual-color staining of FFPE sections for the following antigens: CD4, CD8, CD20, FoxP3, CD68, CD115, Mac387, MRC1, HLA-DR, and PCNA. Nuance multispectral imaging software was used for image acquisition. Protocols for automated image analysis were developed using CellProfiler. Immune cell populations associated with risk of recurrence were identified using classification and regression tree analysis. Results: HG-DCIS had significantly higher percentages of FoxP3+ cells, CD68+ and CD68+PCNA+ macrophages, HLA-DR+ cells, CD4+ T cells, CD20+ B cells, and total tumor infiltrating lymphocytes compared to nHG-DCIS. A classification tree, generated from 16 immune cell populations and 8 clinical parameters, identified three immune cell populations associated with risk of recurrence: CD8+HLADR+ T cells, CD8+HLADR− T cells, and CD115+ cells. Conclusion: These findings suggest that the tumor immune microenvironment is an important factor in identifying DCIS cases with the highest risk for recurrence and that manipulating the immune microenvironment may be an efficacious strategy to alter or prevent disease progression.

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