Analysis of survivin expression in black and white breast cancer patient tissue




Brown, Kerrie
Fang, Yisheng V.
Sankpal, Umesh T.


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Purpose: Survivin is a protein that belongs to the inhibitor of apoptosis family. It inhibits the activation of caspases and is also involved in the regulation of the cell cycle. Survivin is normally expressed during development with no expression detected in most adult differentiated tissues. However, high expression of this protein is found in many cancers which correlates with poor prognosis. Breast cancer disproportionately affects black women who have significantly higher mortality rates compared to white women with breast cancer. We hypothesize that higher expression of Survivin in Black cancer patients correlates with their higher mortality rates. In this project, we compared the level of expression of survivin in breast tumor tissue from Black and White cancer patients. This was done using immunohistochemical (IHC) staining technique of tumor tissue sections and analysis of The Cancer Genome Atlas database. Detecting differential expression of Survivin between the two racial groups and within different subtypes of breast cancer could lead to the development of Survivin as a diagnostic and/or prognostic marker as well as a possible therapeutic target. Methods: Our first approach was to analyze the TCGA database to confirm our hypothesis that there is differential expression of survivin between the two racial groups and within different subtypes of breast cancer. This involved RNA-seq data analysis using various tools available online. Secondly, breast tumor tissue, representing different subtypes of breast cancer, from Black and White patients, was analyzed by immunohistochemistry (IHC) using survivin specific antibodies. The protocol for nuclear and cytoplasmic Survivin detection was standardized. The IHC data, in the form of percent staining (nuclear and cytoplasmic), was then analyzed by semi-quantitative methods using H-score and Allred scores. Results and Conclusions: Results from the analysis of TCGA database and our IHC data indicate significantly higher expression of survivin in tumors from Black patients compared to White. Differential expression was also observed between different subgroups of breast cancer, with high expression in the most aggressive triple negative (TNBC) form of breast cancer. Coincidently, the occurrence of TNBC is higher in Black women compared to White women. We also observed higher nuclear expression in Black patients compared to White patients, which has been associated with poor outcomes. Based on the vast literature suggesting that survivin plays a key role in cancer progression, we believe that survivin could be a useful diagnostic and/or prognostic marker or a therapeutic target to combat the racial disparity in breast cancer.