Stromal Drivers of Ovarian Cancer Initiation
Abstract
Our overall goal is to define how cancer-supportive stromal cells contribute to high grade serous cancer initiation in order to develop improved early diagnostic and therapeutic strategies for high grade serous ovarian cancer. Scope: We proposed three specific aims. Aim 1 is to perform cellular mapping to determine the abundance and spatial relationship of hrMSCs to p53 signature, serous tubal intraepithelial carcinoma (STIC) and invasive cancer in BRCA wild type and BRCA mutant fallopian tubes. Aim 2 is to assess the acquisition of malignancy-associated molecular changes in hrMSC-marked epithelium. Aim 3 is to assess the impact of hrMSCs on epithelial precursor lesion transformation. Major findings: To date, we have collected fallopian tube samples from BRCA wild type and BRCA mutant fallopian tubes and quantified the presence of hrMSCs in 20 samples. We have found hrMSC abundance is correlated with increasing age and is more prevalent in BRCA mutant fallopian tubes. We have obtained matching FFPE tissue and for Vectra multispectral analysis and digital spatial profiling. The Vectra imaging is complete and DSP is being analyzed by the bioinformatics team. Significance: Collectively, our work supports the hypothesis that stromal changes within the fallopian tube support high grade serous ovarian cancer initiation. This work is critical to understanding the pathogenesis of high grade serous ovarian cancer and the development of screening and early detection strategies for this deadly disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1226380
Entities
People
- Lan G. Coffman
Organizations
- University of Pittsburgh