Abstract
Abstract The purpose of this study is to characterize protein markers in African American breast tumors that correspond to different tumor subtypes, recurrence, and survival. Tissue microarrays (TMA) have been used because they have the advantage of analyzing numerous samples on a single slide and can be used in clinical pathology laboratories. Protein markers that have been used are estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), cyclin A2, cytokeratin 5, vimentin, Bcl2, and Ki67. TMA have been prepared and stained for proteins that will distinguish 5 tumor subtypes: luminal A (ER+ and/or PR+ Her2-); luminal B (ER+ and/or PR+ Her2- Cyclin A2+ and/or Ki67+); luminal B Her2+ (ER+ and/or PR+ Her2+); Her2+ (ER- PR- Her2+), and triple negative (ER- PR- Her2-). These subtypes are known to be associated with different relapse-free survival and overall survival. Luminal B tumors have the same ER+PR+HER2- profile as luminal A tumors; however, luminal B tumors have a poor prognosis, whereas luminal A tumors have the best prognosis of all 5 subtypes. Luminal B tumors can be distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 or Ki67, which promote cell proliferation. Cyclin A2 was more frequently expressed than Ki67 in tumors with poor prognosis such as luminal B (ER+PR+HER-) and ER-PR-HER2- (triple negative) tumors. Therefore, Cyclin A2+ may better serve to identify luminal B and triple negative tumors with a poor prognosis and thus aid physicians in treatment decisions. The RASSF1A protein has been reported to inhibit the transcription of Cyclin A2. Methylation of the RASSF1A promoter is expected to decrease RASSF1A transcription and thereby increase Cyclin A2 transcription and protein levels. Significantly increased levels of RASSF1A methylation have been observed in this laboratory with AA ER-PR-HER- breast cancer patients compared to mammoplasty samples. Thus, increased Cyclin A2 protein staining correlated with increased RASSF1A methylation. This is one molecular explanation for elevated cyclin A2 protein levels in triple negative tumors. Discovery of molecular markers and subtypes that are most prevalent in African Americans could lead to a better treatment, targets for therapy, and understanding of the factors contributing to higher mortality in this group compared to other groups. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1699. doi:1538-7445.AM2012-1699
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