Abstract
Abstract Background: Overexpression of Fascin, Endoglin (CD105), and Beta-Catenin has been found to be associated with unfavorable prognosis and progression in hormone-receptor negative breast carcinomas. Specifically, fascin promotes cell motility, while Beta-catenin is involved in cancer invasion, cellular transformation, and metastasis. CD105 is selectively upregulated in small, immature tumor vessels in malignant tumors. The objective of this study was to correlate fascin, CD105, and Beta-Catenin protein expression with clinicopathological factors including age, grade, tumor size, stage, regional node status, survival, and with the four major molecular breast cancer subtypes (luminal A, luminal B, HER2 positive, and Triple Negative [TN]). Methods: Tissue microarrays (TMAs) were constructed from optimally-fixed formalin-fixed, paraffin-embedded tumor blocks from primary breast carcinomas in 203 African-American females. Sections were stained with antitibodies against fascin, CD105, and beta-catenin. The sections were evaluated for the intensity of reactivity (0-3) and the percentage of reactive cells. Cases were categorized as having negative/weak (score <10) or moderate/strong (score >10) fascin expression, negative (score=0) or positive (score>0) CD105 (in tumor cells only) and beta-catenin (cytoplasmic and nuclear) expression. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). Statistical significance was assumed if P < 0.05. Results: On the TMA, there were 67 triple negatives, 88 Luminal As, 29 Luminal Bs, and 18 Her2 overexpressing cancers. The mean age for the patients in the study was 57.65. Fascin expression was significantly linked to the triple negative subtype (p<0.0001), ER negativity (p<0.0001), PR negativity (0.0001), and Grade III differentiation (p=0.03). CD105 cytoplasmic expression significantly correlated with HER2 positive subtype (p<0.0001), Luminal B subtype (0.01), HER2 positivity (p<0.0001), tumor size (p<0.01) and was associated with decreased disease-free survival (p=0.038). Cytoplasmic beta-catenin expression was significantly associated with triple negative subtype (p<0.03), HER2+ subtype (p<0.001), ER negativity (p<0.001), PR negativity (p<0.001), and HER2 negativity (p=0.03). Conclusions: Our results indicate that fascin, CD105, and Beta-catenin may be potential markers of aggressive breast cancer subtypes and predictors of recurrence and survival. These data also support pharmacological targets for these aggressive subtypes. 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 692. doi:1538-7445.AM2012-692
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