Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast
dc.contributor.author | Badve, Sunil S. | |
dc.contributor.author | Cho, Sanghee | |
dc.contributor.author | Gökmen-Polar, Yesim | |
dc.contributor.author | Sui, Yunxia | |
dc.contributor.author | Chadwick, Chrystal | |
dc.contributor.author | McDonough, Elizabeth | |
dc.contributor.author | Sood, Anup | |
dc.contributor.author | Taylor, Marian | |
dc.contributor.author | Zavodszky, Maria | |
dc.contributor.author | Tan, Puay Hoon | |
dc.contributor.author | Gerdes, Michael | |
dc.contributor.author | Harris, Adrian L. | |
dc.contributor.author | Ginty, Fiona | |
dc.contributor.department | Pathology and Laboratory Medicine, School of Medicine | en_US |
dc.date.accessioned | 2023-04-24T14:38:11Z | |
dc.date.available | 2023-04-24T14:38:11Z | |
dc.date.issued | 2021 | |
dc.description.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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Badve SS, Cho S, Gökmen-Polar Y, et al. Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast. Br J Cancer. 2021;124(6):1150-1159. doi:10.1038/s41416-020-01216-6 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/32558 | |
dc.language.iso | en_US | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.isversionof | 10.1038/s41416-020-01216-6 | en_US |
dc.relation.journal | British Journal of Cancer | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | Breast cancer | en_US |
dc.subject | Prognostic markers | en_US |
dc.subject | Mastectomy | en_US |
dc.subject | Breast neoplasms | en_US |
dc.subject | Survival rate | en_US |
dc.title | Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast | en_US |
dc.type | Article | en_US |