CD105 (Endoglin) Expression in Tumor Cells Associated with HER2 Positive Breast Cancers and Decreased Disease-Free Survival in African American Women
Tammey J Naab, Luisel J Ricks-Santi, Yasmine M Kannan, Ashwini K Esnakula. Howard University Hospital, Washington, DC; Howard University Cancer Center, Washington, DC
Background: CD105(Endoglin) is a membrane glycoprotein and functions as a component of the transforming growth factor-β receptor complex. Its expression is selectively upregulated in small, immature tumor vessels in malignant tumors. High grade malignant tumors, e.g., melanoma cells and ovarian serous carcinoma cells, have shown cytoplasmic CD105 expression. The significance of CD105 cytoplasmic expression in human breast cancer has not been established. The object of our study is to evaluate the association of CD105 cytoplasmic expression in tumor cells in the four major subtypes (Luminal A, Lumina B, HER2 positive, Triple Negative) and other clinicopathological factors including age, grade, tumor size, stage, regional node status, and disease-free survival in African American women.
Design: Tissue microarrays were constructed from optimally-fixed formalin-fixed, paraffin-embedded tumor blocks from primary breast carcinomas in 202 African-American females. Two separate 1mm cores represented each case. Five micrometer sections were stained with a mouse monoclonal antibody against CD105 (4G11, Leica, IL, USA). The sections were evaluated for the intensity of reactivity (0-3) and the percentage of reactive cells; an H-score was derived from the product of these measurements. Cases were categorized as having negative (score=0) or positive (score>0) cytoplasmic expression in tumor cells. 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: CD105 cytoplasmic tumor cell expression significantly correlated with HER2+ subtype (p<0.0001), Luminal B subtype (p<0.01), tumor Size (p<0.01), HER2 positivity (p<0.0001) and decreased disease-free survival (p=0.038). No correlation was seen with tumor cell CD105 cytoplasmic expression and other prognostic parameters.
Conclusions: Our results show a significant correlation of CD105 cytoplasmic expression with HER2+ subtypes and decreased disease-free survival. In animal models and in vitro studies, anti-CD105 monoclonal antibodies induced regression of preformed tumors and inhibited formation of new tumors. In women with HER2+ breast cancers, targeted therapy with anti-CD105 mAbs could potentially attack not only tumors with high microvessel density but also the breast cancer cells as well.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 26, Tuesday Morning