Date of Award
Master of Science (MS)
Breast cancer is the most common cancer in women in the United States and is thesecond highest cause of cancer death in women. The rise in available screening techniques over the years has led to earlier detection of breast cancer, which has in turn allowed for more effective treatments and better prognoses. However, there is unintended harm associated with increased screening. There have been increased numbers of ductal carcinoma in situ (DCIS) which is a non-obligate precursor of invasive breast cancer. Currently there is no reliable method to predict which DCIS cases will progress to invasive breast cancer. It is critical to identify factors that predict progression and recurrence to make sure patients receive appropriate treatment. The tumor microenvironment has been suggested as playing a role in DCIS progression and recurrence. Gene profiling has identified changes that occur in the microenvironment during progression. In the past, it has been difficult to understand how cells within the microenvironment are interacting with the tumor cells because of technological limitations. With the increase in high-throughput “spatial-omics” technologies, it is now possible to phenotype cells and understand how they are spatially interacting with the tumor. The goal of this study is to spatially profile the microenvironment around normal/benign breast, DCIS, and invasive breast cancer samples to identify potential biomarkers of progression and recurrence. Archival specimens from several different groups of patient samples were stained with multiplex fluorescence in situ hybridization (FISH) and high-plex immunofluorescence panels and analyzed to identify different types of cells within the epithelium and stroma and how they were spatially located with respect to the tumor. We identified myoepithelial continuity within the ducts as one of the features that may influence progression of the disease. Cells within stromal microenvironment that are either expressing transcription factors (RUNX1), long non-coding RNA (MANCR), chemokine receptors and ligands (CXCR6, CXCL12), mesenchymal stromal cell marker (CD90), and myoepithelial marker (TP63) were associated with various clinical factors including grade, HER2 status, hormone receptor status, differentiation, type of DCIS, and lymphatic vascular invasion. Future studies to confirm the importance of myoepithelial continuity measurement to predict recurrence and whole transcriptome analyses to correlate RNA with markers phenotyping the cells will provide a better understanding of how the tumor microenvironment functions in breast cancer progression and recurrence.
Number of Pages
Lee, Kyra, "High-Plex Imaging Of Rnas And Proteins For Spatial Profiling Of The Breast Cancer Tumor Microenvironment" (2024). Graduate College Dissertations and Theses. 1805.
Available for download on Sunday, December 07, 2025