Tissue Microarray-Based Digital Spatial Profiling of Benign Breast Lobules and Breast Cancers: Feasibility, Biological Coherence, and Cross-Platform Benchmarks
Mark E. Sherman, Jodi C. Carter, Robert A. Vierkant, Melody Stallings-Mann, Laura Pacheco-Spann, Stacey J. Winham, Celine M. Vachon, Chen Wang, Matthew R. Jensen, Melissa A. Troester, Amy C. Degnim, E. Aubrey Thompson, Jennifer Kachergus, Ji Shi, Derek C. Radisky, Cristian Scatena, Carmine De Angelis
Abstract
Title: Simple Summary Most breast biopsies show non-cancerous (benign) changes, yet some women later develop breast cancer. Predicting who is at higher risk from these small tissue samples is difficult because the relevant structures are tiny and easily exhausted by testing. We evaluated whether a multiplex technology called digital spatial profiling can measure many proteins at once on tissue microarrays built from benign breast lobules, nearby tissue next to cancers, and cancers themselves. We also compared the results to standard lab tests. The approach worked well overall and reproduced known biology, especially in cancer tissue. Signals in benign lobules were more variable and did not, on their own, distinguish women who later developed cancer from matched controls in this pilot. These findings show that high-plex, tissue-conserving profiling is feasible and biologically coherent, and they outline concrete ways to improve sampling and marker panels for future risk-prediction studies.

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