title: Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Surgery, University of California, 2340 Sutter St, N321, San Francisco, CA, 94115, USA. michael.campbell@ucsf.edu.
authors: Michael J
authors: MJ
authors: Campbell
authors: Department of Pathology, University of California, San Francisco, CA, USA.
authors: Frederick
authors: F
authors: Baehner
authors: Mt Zion Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors: Tess
authors: T
authors: O'Meara
authors: Mt Zion Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors: Ekene
authors: E
authors: Ojukwu
authors: Mt Zion Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors: Booyeon
authors: B
authors: Han
authors: Department of Surgery, University of California, 2340 Sutter St, N321, San Francisco, CA, 94115, USA.
authors: Rita
authors: R
authors: Mukhtar
authors: Mt Zion Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors: Vickram
authors: V
authors: Tandon
authors: Mt Zion Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors: Max
authors: M
authors: Endicott
authors: Mt Zion Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors: Zelos
authors: Z
authors: Zhu
authors: Department of Surgery, University of California, 2340 Sutter St, N321, San Francisco, CA, 94115, USA.
authors: Jasmine
authors: J
authors: Wong
authors: Department of Pathology, University of California, San Francisco, CA, USA.
authors: Gregor
authors: G
authors: Krings
authors: Department of Pathology, University of California, San Francisco, CA, USA.
authors: Alfred
authors: A
authors: Au
authors: Oregon Health and Science University, Portland, OR, USA.
authors: Joe W
authors: JW
authors: Gray
authors: Department of Surgery, University of California, 2340 Sutter St, N321, San Francisco, CA, 94115, USA.|Mt Zion Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors: Laura
authors: L
authors: Esserman
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D047368:Tumor Burden; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D015415:Biomarkers
keywords: Breast; DCIS; Immune microenvironment