Breast Cancer Research and Treatment

, Volume 164, Issue 2, pp 305–315

Image analysis of immune cell patterns in the human mammary gland during the menstrual cycle refines lymphocytic lobulitis

  • Nadine S. Schaadt
  • Juan Carlos López Alfonso
  • Ralf Schönmeyer
  • Anne Grote
  • Germain Forestier
  • Cédric Wemmert
  • Nicole Krönke
  • Mechthild Stoeckelhuber
  • Hans H. Kreipe
  • Haralampos Hatzikirou
  • Friedrich Feuerhake
Preclinical study

Abstract

Purpose

To improve microscopic evaluation of immune cells relevant in breast cancer oncoimmunology, we aim at distinguishing normal infiltration patterns from lymphocytic lobulitis by advanced image analysis. We consider potential immune cell variations due to the menstrual cycle and oral contraceptives in non-neoplastic mammary gland tissue.

Methods

Lymphocyte and macrophage distributions were analyzed in the anatomical context of the resting mammary gland in immunohistochemically stained digital whole slide images obtained from 53 reduction mammoplasty specimens. Our image analysis workflow included automated regions of interest detection, immune cell recognition, and co-registration of regions of interest.

Results

In normal lobular epithelium, seven CD8\(^{+}\) lymphocytes per 100 epithelial cells were present on average and about 70% of this T-lymphocyte population was lined up along the basal cell layer in close proximity to the epithelium. The density of CD8\(^{+}\) T-cell was 1.6 fold higher in the luteal than in the follicular phase in spontaneous menstrual cycles and 1.4 fold increased under the influence of oral contraceptives, and not co-localized with epithelial proliferation. CD4\(^{+}\) T-cells were infrequent. Abundant CD163\(^{+}\) macrophages were widely spread, including the interstitial compartment, with minor variation during the menstrual cycle.

Conclusions

Spatial patterns of different immune cell subtypes determine the range of normal, as opposed to inflammatory conditions of the breast tissue microenvironment. Advanced image analysis enables quantification of hormonal effects, refines lymphocytic lobulitis, and shows potential for comprehensive biopsy evaluation in oncoimmunology.

Keywords

Lymphocytic lobulitis Digital pathology Oncoimmunology Object-based image analysis Menstrual cycle Hormonal fluctuations 

Supplementary material

10549_2017_4239_MOESM1_ESM.pdf (16.3 mb)
(PDF 16,705 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Nadine S. Schaadt
    • 1
  • Juan Carlos López Alfonso
    • 3
  • Ralf Schönmeyer
    • 4
  • Anne Grote
    • 1
  • Germain Forestier
    • 5
  • Cédric Wemmert
    • 2
  • Nicole Krönke
    • 1
  • Mechthild Stoeckelhuber
    • 6
  • Hans H. Kreipe
    • 1
  • Haralampos Hatzikirou
    • 3
  • Friedrich Feuerhake
    • 1
    • 7
  1. 1.Institute of Pathology, NeuropathologyHannover Medical SchoolHannoverGermany
  2. 2.ICubeUniversity of StrasbourgIllkirchFrance
  3. 3.Department of Systems Immunology and Braunschweig Integrated Centre of Systems BiologyHelmholtz Centre for Infection Research38124 BraunschweigGermany
  4. 4.Definiens AGMunichGermany
  5. 5.MIPSUniversity of Haute AlsaceMulhouseFrance
  6. 6.Department of Oral and Maxillofacial SurgeryTechnische Universität MünchenMunichGermany
  7. 7.University Clinic of FreiburgInstitute for NeuropathologyFreiburgGermany

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