A method for quantification of calponin expression in myoepithelial cells in immunohistochemical images of ductal carcinoma in situ

Elliot Gray, Elizabeth Mitchell, Sonali Jindal, Pepper Schedin, Young Hwan Chang
2018 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018)  
Ductal carcinoma in situ (DCIS) is breast cancer confined within mammary ducts, surrounded by an intact myoepithelial cell layer that prevents local invasion. A DCIS diagnosis confers increased lifetime risk of developing invasive breast cancer (IBC) and results in surgical excision with radiation, and possibly endocrine-or chemo-therapy. DCIS is known to be over treated, with associated co-morbidities. Biomarkers are needed that delineate patients at low risk of DCIS progression from patients
more » ... equiring more aggressive treatment. Investigating the role of myoepithelial cell differentiation in barrier function is anticipated to provide insight into DCIS progression and delineate between low and high risk lesions. Here, we develop a high throughput technique to assess loss of myoepithelial differentiation markers. This method facilitates automated analysis of a clinically relevant histopathologic feature, as demonstrated by a high correlation with pathologist annotation (r = 0.959), and further, contributes analytical foundations to a multiplexed immunohistochemistry (IHC) approach. Keywords DCIS; calponin; invasive breast cancer; feature engineering; myoepithelial cell DCIS AND INVASIVE BREAST CANCER Incidence of ductal carcinoma in situ (DCIS) increased from 3% in the early 1970's to ~20% of all breast cancers due to widespread use of screening mammography [1] . This year in the U.S., ~50,000 women will be diagnosed with DCIS. DCIS carries an increased lifetime risk of invasive breast cancer (IBC) with long term studies of untreated DCIS showing 30% progression to IBC [2] . Unfortunately, the clinical accuracy to predict which DCIS will remain indolent and which will progress to IBC remains low, leaving an urgent need to discover biomarkers of progression. The myoepithelial cell is a 'gate keeper' to breast cancer invasion through the mammary duct, exerting tumor suppressive effects by secreting tumor suppressive proteins and by forming a physical barrier that prevents tumor cell escape [3] [4] [5] [6] . Variable expression of myoepithelial differentiation markers such as calponin and α-smooth muscle actin (αSMA) are reported in DCIS cases, while physical gaps in the myoepithelium or its loss are used
doi:10.1109/isbi.2018.8363692 pmid:30364524 pmcid:PMC6196724 dblp:conf/isbi/GrayMJSC18 fatcat:kysvs2hipndsrewll3mdsa5nbq