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Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ
Author(s) -
Boecker Werner,
Moll Roland,
Dervan Peter,
Buerger Horst,
Poremba Christopher,
Diallo Raihanatou Ina,
Herbst Hermann,
Schmidt Ansgar,
Lerch Markus M,
Buchwalow Igor B
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1241
Subject(s) - myoepithelial cell , ductal carcinoma , pathology , progenitor cell , hyperplasia , stem cell , biology , ductal cells , progenitor , breast cancer , medicine , cancer , immunohistochemistry , microbiology and biotechnology , genetics
Current classification systems in proliferative mammary gland pathology are based on a two‐cell system, recognizing only glandular and myoepithelial lines of differentiation. A third cell type has recently been characterized in normal breast tissue by double‐immunofluorescence analysis to express cytokeratin 5 (Ck5) only. These cells were shown to represent progenitor or adult stem cells that give rise to the glandular and myoepithelial cell lineage. The double‐labelling technique has been applied to characterize a spectrum of intraductal epithelial proliferations, namely benign usual ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ , all of which are thought to represent the gradual steps of a sequence in the development of breast cancer. Immunofluorescence studies with specific antibodies against Ck5, Ck8/18/19, and smooth muscle actin were complemented by western blotting analysis of Ck5 and Ck8/18/19 expression in normal breast tissue and in proliferative lesions. Usual ductal hyperplasia appears to be a Ck5‐positive committed stem (progenitor) cell lesion with the same differentiation potential as seen in the normal breast. This is in sharp contrast to atypical ductal hyperplasia/ductal carcinoma in situ , which display the differentiated glandular immunophenotype (Ck8/18/19‐positive, but Ck5‐negative). These data require the abandonment of the idea of an obligate biological continuum of intraductal proliferations from benign to malignant. This study provides evidence that cells undergoing malignant transformation tend to be fairly advanced in the glandular lineage of differentiation. The committed stem (progenitor) cell model may contribute to a better understanding of both benign proliferative breast disease and breast cancer development. Copyright © 2002 John Wiley & Sons, Ltd.