Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast. 2021

Sunil S Badve, and Sanghee Cho, and Yesim Gökmen-Polar, and Yunxia Sui, and Chrystal Chadwick, and Elizabeth McDonough, and Anup Sood, and Marian Taylor, and Maria Zavodszky, and Puay Hoon Tan, and Michael Gerdes, and Adrian L Harris, and Fiona Ginty
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. sbadve@iupui.edu.

There is limited knowledge about DCIS cellular composition and relationship with breast cancer events (BCE). 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. 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). 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.

UI MeSH Term Description Entries
D008408 Mastectomy Surgical procedure to remove one or both breasts. Mammectomy,Mammectomies,Mastectomies
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002285 Carcinoma, Intraductal, Noninfiltrating A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma. Carcinoma, Intraductal,DCIS,Ductal Carcinoma In Situ,Atypical Ductal Hyperplasia,Intraductal Carcinoma, Noninfiltrating,Atypical Ductal Hyperplasias,Carcinoma, Noninfiltrating Intraductal,Carcinomas, Intraductal,Carcinomas, Noninfiltrating Intraductal,Ductal Hyperplasia, Atypical,Ductal Hyperplasias, Atypical,Hyperplasia, Atypical Ductal,Hyperplasias, Atypical Ductal,Intraductal Carcinoma,Intraductal Carcinomas,Intraductal Carcinomas, Noninfiltrating,Noninfiltrating Intraductal Carcinoma,Noninfiltrating Intraductal Carcinomas
D003131 Combined Modality Therapy The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used. Multimodal Treatment,Therapy, Combined Modality,Combined Modality Therapies,Modality Therapies, Combined,Modality Therapy, Combined,Multimodal Treatments,Therapies, Combined Modality,Treatment, Multimodal,Treatments, Multimodal
D005260 Female Females
D005500 Follow-Up Studies Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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