Cytoplasmic Beta-Catenin Expression Associated with Triple Negative and HER2 Positive Breast Cancer Subtypes in African-American Women
Ashwini K Esnakula, Luisel J Ricks-Santi, Yasmine M Kannan, Tammey J Naab. Howard University Hospital, Washington, DC; Howard University Cancer Center, Washington, DC
Background: Beta-catenin plays an essential role in cell adhesion via catenin-cadherin complexes and acts as a transcriptional regulator in the Wnt signaling pathway. With Wnt activation, beta-catenin is transferred from the membrane to the cytoplasm and the nucleus where it interacts with activators of transcription to modulate target genes, including c-MYC and cyclin D1, responsible for growth, invasion, and cellular transformation. The object of our study is to look for an association between beta-catenin expression and prognostic factors in four major subtypes of breast cancer (Luminal A, Luminal B, HER2 positive, Triple Negative) in 202 African-American women.
Design: Tissue microarrays (TMAs) 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 polyclonal antibody against beta-catenin (17C2, Thermo, CA, USA). The sections were evaluated for 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 <100) or positive (score ≥100) for membrane expression and negative (score=0) or positive (score>0) for cytoplasmic expression and nuclear expression. Bivariate analysis was done separately for the membrane expression and the cytoplasmic expression 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: Cytoplasmic beta-catenin expression was associated with the HER2+ subtype (p<0.001), ER negativity (p<0.001), PR negativity (p<0.001), the Triple Negative subtype (p<0.03), and HER2 positivity (p=0.03). No correlation was seen with cytoplasmic beta-catenin expression and age, tumor size, node status, stage, grade, or survival. No correlation was found with loss or retention of beta-catenin membrane expression and any prognostic parameters. No nuclear stain was observed in any case.
Conclusions: Our study found a significant association between the beta-catenin cytoplasmic expression and the breast cancer subtypes, HER2+ and Triple Negative and hormone negative cancers. Collectively, these findings suggest that Wnt signalling pathway may play a role in the pathogenesis of unfavorable breast cancer subtypes in African-American females.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 42, Wednesday Morning