Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast

• Type of Material: Article
• Authors: Sunil Badve, Emory University; Sanghee Cho, GE Research; Yesim Polar, Emory University; Yunxia Sui, GE Research; Chrystal Chadwick, GE Research; Elizabeth McDonough, GE Research; Anup Sood, GE Research; Marian Taylor, University of Oxford; Maria Zavodszky, GE Research; Puay Hoon Tan, Singapore General Hospital; Michael Gerdes, GE Research; Adrian L. Harris, University of Oxford; Fiona Ginty, GE Research
• Language: English
• Date: 2021-01-07
• Publisher: SPRINGERNATURE
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s), under exclusive licence to Cancer Research UK 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41416-020-01216-6
• Title of Journal or Parent Work: BRITISH JOURNAL OF CANCER
• Volume: 124
• Issue: 6
• Start Page: 1150
• End Page: 1159
• Grant/Funding Information: This study is supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA194600 to S. Badve, M. Gerdes and F. Ginty. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: EXPRESSION; RISK; INTERNATIONAL MULTICENTER; LOCAL RECURRENCE; CANCER MORTALITY; ACTIVE SURVEILLANCE; Life Sciences & Biomedicine; Science & Technology; Oncology; BIOPSY; WOMEN; OVERDIAGNOSIS; HETEROGENEITY
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Oncology

Abstract

Background: There is limited knowledge about DCIS cellular composition and relationship with breast cancer events (BCE). Methods: Immunofluorescence multiplexing (MxIF) was used to image and quantify 32 cellular biomarkers in FFPE DCIS tissue microarrays. Over 75,000 DCIS cells from 51 patients (median 9 years follow-up for non-BCE cases) were analysed for profiles predictive of BCE. K-means clustering was used to evaluate cellular co-expression of epithelial markers with ER and HER2. Results: Only ER, PR and HER2 significantly correlated with BCE. Cluster analysis identified 6 distinct cell groups with different levels of ER, Her2, cMET and SLC7A5. Clusters 1 and 3 were not significant. Clusters 2 and 4 (high ER/low HER2 and SLC7A5/mixed cMET) significantly correlated with low BCE risk (P = 0.001 and P = 0.034), while cluster 6 (high HER2/low ER, cMET and SLC7A5) correlated with increased risk (P = 0.018). Cluster 5 (similar to cluster 6, except high SLC7A5) trended towards significance (P = 0.072). A continuous expression score (Escore) based on these 4 clusters predicted likelihood of BCE (AUC = 0.79, log-rank test P = 5E–05; LOOCV AUC = 0.74, log-rank test P = 0.006). Conclusion: Multiplexed spatial analysis of limited tissue is a novel method for biomarker analysis and predicting BCEs. Further validation of Escore is needed in a larger cohort.