Myoepithelial cell differentiation markers in ductal carcinoma in situ progression.

Abstract

We describe a preclinical model that investigates progression of early-stage ductal carcinoma in situ (DCIS) and report that compromised myoepithelial cell differentiation occurs before transition to invasive disease. Human breast cancer MCF10DCIS.com cells were delivered into the mouse mammary teat by intraductal injection in the absence of surgical manipulations and accompanying wound-healing confounders. DCIS-like lesions developed throughout the mammary ducts with full representation of human DCIS histologic patterns. Tumor cells were incorporated into the normal mammary epithelium, developed ductal intraepithelial neoplasia and DCIS, and progressed to invasive carcinoma, suggesting the model provides a rigorous approach to study early stages of breast cancer progression. Mammary glands were evaluated for myoepithelium integrity with immunohistochemical assays. Progressive loss of the myoepithelial cell differentiation markers p63, calponin, and α-smooth muscle actin was observed in the mouse myoepithelium surrounding DCIS-involved ducts. p63 loss was an early indicator, calponin loss intermediate, and α-smooth muscle actin a later indicator of compromised myoepithelium. Loss of myoepithelial calponin was specifically associated with gain of the basal marker p63 in adjacent tumor cells. In single time point biopsies obtained from 16 women diagnosed with pure DCIS, a similar loss in myoepithelial cell markers was observed. These results suggest that further research is warranted into the role of myoepithelial cell p63 and calponin expression on DCIS progression to invasive disease.

• Authors: Tanya D Russell, Sonali Jindal, Samiat Agunbiade, Dexiang Gao, Megan Troxell, Virginia F Borges, Pepper Schedin
• Journal: The American journal of pathology (Am J Pathol) Vol. 185 Issue 11 Pg. 3076-89 (Nov 2015) ISSN: 1525-2191 [Electronic] United States
• PMID: 26343330 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Differentiation
• Biomarkers, Tumor
• CKAP4 protein, human
• Calcium-Binding Proteins
• Membrane Proteins
• Microfilament Proteins
• Phosphoproteins
• Trans-Activators
• Trp63 protein, mouse
• calponin

Topics

• Animals
• Antigens, Differentiation
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (metabolism, pathology)
• Calcium-Binding Proteins (genetics, metabolism)
• Carcinoma, Intraductal, Noninfiltrating (metabolism, pathology)
• Disease Progression
• Epithelial Cells (metabolism, pathology)
• Epithelium (pathology)
• Female
• Humans
• Membrane Proteins (genetics, metabolism)
• Mice
• Microfilament Proteins (genetics, metabolism)
• Phosphoproteins (genetics, metabolism)
• Trans-Activators (genetics, metabolism)