title: 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.
abstract: 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.
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University of Muenster, 48149, Muenster, Germany. boecker@me.com.|Gerhard-Seifert Referenzzentrum, Papenreye 23, 22455, Hamburg, Germany. boecker@me.com.
authors.forename: Werner
authors.initials: W
authors.lastname: Boecker
authors.affiliation: Sahlgrenska Cancer Center, University of Gothenburg, 405 30, Gothenburg, SE, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Stenman
authors.affiliation: Institute for Anatomy and Experimental Morphology, University of Hamburg, 20246, Hamburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: Institute for Anatomy and Experimental Morphology, University of Hamburg, 20246, Hamburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.affiliation: Gerhard-Seifert Referenzzentrum, Papenreye 23, 22455, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Loening
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University of Muenster, 48149, Muenster, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Stahnke
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University of Muenster, 48149, Muenster, Germany.
authors.forename: Catharina
authors.initials: C
authors.lastname: Löhnert
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University of Muenster, 48149, Muenster, Germany.
authors.forename: Robert Michael
authors.initials: RM
authors.lastname: Siering
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University of Muenster, 48149, Muenster, Germany.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kuper
authors.affiliation: Institute for Hematopathology, 22547, Hamburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Samoilova
authors.affiliation: Institute for Hematopathology, 22547, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Tiemann
authors.affiliation: Institute of Bioinformatics, University of Muenster, 48149, Muenster, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Korsching
authors.affiliation: Institute for Hematopathology, 22547, Hamburg, Germany. buchwalow@pathologie-hh.de.
authors.forename: Igor
authors.initials: I
authors.lastname: Buchwalow
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology*; D002278:Carcinoma in Situ / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D011230:Precancerous Conditions / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; C081876:CKAP4 protein, human; C030659:K antigens; D008565:Membrane Proteins
keywords: Low-grade intraepithelial neoplasias; Luminal cells; Normal breast epithelium; Usual ductal hyperplasia; p63+K5+ progenitor cells