Loss of myoepithelial calponin-1 characterizes high-risk ductal carcinoma in situ cases, which are further stratified by T cell composition

Molecular Carcinogenesis
Elizabeth MitchellPepper Schedin

Abstract

A hallmark of ductal carcinoma in situ (DCIS) progression is a loss of the surrounding ductal myoepithelium. However, whether compromise in myoepithelial differentiation, rather than overt cellular loss, can be used to predict the risk of DCIS progression is unknown. Here we address this question utilizing pure and mixed DCIS cases (N = 30) as surrogates for DCIS at low and high risk for progression, respectively. We used multiplex immunohistochemical staining to evaluate the relationship between myoepithelial cell differentiation and lymphoid immune cell types associated with poor prognostic DCIS. Our results show that myoepithelial calponin-1 discriminates between pure and mixed DCIS lesions better than histological subtype, presence of necrosis, or nuclear grade. Additionally, focal loss of myoepithelial cells associated with increased PD-1+CD8+ T cells, which suggests a link between the myoepithelium and immune surveillance. To identify associations between calponin-1 expression and immune response, we performed unsupervised hierarchical clustering of myoepithelial and immune cell biomarkers on 219 DCIS lesions from 30 cases. Notably, the majority of pure (low-risk) DCIS lesions clustered in a high calponin-1, T cell low gr...Continue Reading

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Citations

May 10, 2020·Molecular Carcinogenesis·Yong-Chen Lu, Xiao-Jing Wang
Apr 29, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Marie Colombe AgahozoCarolien H M van Deurzen

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Methods Mentioned

BETA
SMA
Profiler
FCS
flow cytometry

Software Mentioned

GraphPad Prism
FIJI
morphologyEx
Matlab
Cell Profiler
CellProfiler
R
heatmap3
FCS Express 6 Image Cytometry RUO
Studio

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