Description
Globally, prostate cancer is the most common invasive malignancy and the sixth leading cause of cancer-related death in men. Prostate cancer incidence is significantly higher in the United States compared to most other countries, due to dietary and environmental factors. Well-established risk factors for prostate cancer include increasing age, African ancestry, and a family history of prostate cancer_. African Americans have a higher incidence at a younger age, more aggressive forms of the disease, and shortest survival for all major cancers, and disparities persist despite an improved understanding of early detection, genetics, and socioeconomic risk factors_. Ethnicity/race is the major risk factor, after adjusting for age in this type of cancer. In prostate cancer, the tumor microenvironment (stroma) is considered to be a niche which favors tumor cell proliferation, survival, invasion, and metastasis_. Interaction with cancer cells can lead to genetic changes in stroma cells. Active stromal components mostly contain smooth muscle cells, fibroblasts, vascular endothelial cells, carcinoma-associated fibroblasts, and inflammatory cells_. Cancer-associated fibroblasts are functionally and structurally different from fibroblasts, which exist adjacent to the normal epithelium. These cells, when mixed with normal prostate epithelial cells, can induce their malignant transformation_. Microarray analyses have identified pathways that are significantly associated with tumor and stromal tissues in prostate cancer_. 20% of these pathways are extracellular matrix components, cell adhesion molecules, and epithelial to mesenchymal transition_. In addition previous studies analyzing microarray data showed significantly modified gene expression between African American and Caucasian American stromal tissue_. Tissue microarrays are a useful technique for profiling protein expression in a large number of samples and is applied in this thesis project for the purpose of the microarray results optimization, validation, and its racial disparity outcomes in prostate cancer, as well as to determine if products of differentially expressed genes in tumor versus stroma of prostate cancer tissues follow the same pattern as transcript levels. We were going to quantify the proteins of interest using immunohistochemistry in an independent cohort of African American and Caucasian American prostate cancer samples.
