Fascin Expression Associated with Triple Negative Breast Cancers and Unfavorable Prognosis in African-American Women
Ashwini K Esnakula, Luisel J Ricks-Santi, Wayne Frederick, Tammey J Naab. Howard University Hospital, Washington, DC; Howard University Cancer Center, Washington, DC
Background: Fascin, an actin-binding protein, induces parallel actin bundles in cell protrusions and promotes cell motility. Fascin overexpression has been associated with progression and unfavorable prognosis in hormone-receptor negative breast carcinomas. The objective of our study is to correlate the immunohistochemical expression of fascin in the four major subtypes of breast carcinoma (luminal A, luminal B, HER2 positive, and Triple Negative) and other clinicopathological factors including age, grade, tumor size, stage, regional node status, and overall survival in African American women.
Design: Tissue microarrays (TMAs) were constructed from optimally-fixed formalin-fixed, paraffin-embedded tumor blocks from primary breast carcinomas in 203 African-American females. Two separate 1mm cores represented each case. Five micrometer sections were stained with a primary monoclonal antibody against fascin (FCN01, Thermo, CA, USA). The sections were evaluated for the intensity of reactivity (0-3) and the percentage of reactive cells; and an H-score was derived from the product of these measurements. Cases were categorized as having negative/weak (score ≤100) or moderate/strong (score >100) fascin 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: 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). There was a trend towards decreased overall survival (p=0.08) and disease-free survival (p=0.05). No correlation was seen with fascin expression and age, tumor size, node status, or stage.
Conclusions: Our results indicate that fascin could be a potential marker of aggressive phenotype and a predictor of recurrence. Recent in vitro studies reveal that migrastatin analogs inhibit cell migration and metastasis by targeting fascin, making fascin a potential molecular target for cancer treatment in patients with Triple Negative breast carcinoma.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 25, Tuesday Morning