TY - JOUR
T1 - Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast
AU - Campbell, Michael J.
AU - Baehner, Frederick
AU - O’Meara, Tess
AU - Ojukwu, Ekene
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 W.
AU - Esserman, Laura
N1 - Funding Information:
This work was supported by the Breast Cancer Research Foundation (Esserman), the National Institutes of Health, National Cancer Institute Grant P50 CA 58207 (Gray), and the Department of the Army, award: W81XWH-07-1-0663 and W81XWH-11-1-0549-BC100597P1 (Esserman, Gray, Baehner). The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding and administering acquisition office. The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.
PY - 2017/1/1
Y1 - 2017/1/1
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.
KW - Breast
KW - DCIS
KW - Immune microenvironment
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U2 - 10.1007/s10549-016-4036-0
DO - 10.1007/s10549-016-4036-0
M3 - Article
C2 - 27785654
AN - SCOPUS:84992406238
VL - 161
SP - 17
EP - 28
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 1
ER -