Virchows Archiv

, Volume 470, Issue 5, pp 493–504 | Cite as

Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast

  • Werner Boecker
  • Göran Stenman
  • Tina Schroeder
  • Udo Schumacher
  • Thomas Loening
  • Lisa Stahnke
  • Catharina Löhnert
  • Robert Michael Siering
  • Arthur Kuper
  • Vera Samoilova
  • Markus Tiemann
  • Eberhard Korsching
  • Igor Buchwalow
Original Article


We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.


Normal breast epithelium Usual ductal hyperplasia Low-grade intraepithelial neoplasias p63+K5+ progenitor cells Luminal cells 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Werner Boecker
    • 1
    • 4
  • Göran Stenman
    • 2
  • Tina Schroeder
    • 3
  • Udo Schumacher
    • 3
  • Thomas Loening
    • 4
  • Lisa Stahnke
    • 1
  • Catharina Löhnert
    • 1
  • Robert Michael Siering
    • 1
  • Arthur Kuper
    • 1
  • Vera Samoilova
    • 5
  • Markus Tiemann
    • 5
  • Eberhard Korsching
    • 6
  • Igor Buchwalow
    • 5
  1. 1.Gerhard-Domagk-Institute of PathologyUniversity of MuensterMuensterGermany
  2. 2.Sahlgrenska Cancer CenterUniversity of GothenburgGothenburgSweden
  3. 3.Institute for Anatomy and Experimental MorphologyUniversity of HamburgHamburgGermany
  4. 4.Gerhard-Seifert ReferenzzentrumHamburgGermany
  5. 5.Institute for HematopathologyHamburgGermany
  6. 6.Institute of BioinformaticsUniversity of MuensterMuensterGermany

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