High Claudin-4 Expression in Triple Negative Breast Carcinomas from African-American Women
Tammey J Naab, Luisel J Ricks-Santi, Desta Beyene, Carolyn Broome, Ashwini K Esnakula. Howard University, Washington, DC
Background: Progressive growth of breast cancer cells is associated with alterations in the cell-cell and cell-matrix adhesions leading to disorganized growth with loss of polarity. The claudin family has an integral role in tight junctions, the apically located cell-cell adhesion complex. Claudin-4 binds to cytoplasmic tight junction proteins interacting with signaling pathways, and to actin filaments, which alter cell polarity and cell motility. Overexpression of claudin-4 in primary breast carcinomas has been associated with poor prognosis and high tumor grade. Our study is undertaken to analyze the expression of claudin-4 in the four main subtypes of breast cancer (Luminal A, Luminal B, HER2 positive, triple negative) and correlate with clinicopathological factors in African-American women.
Design: Tissue microarrays (TMAs) were constructed from optimally-fixed formalin-fixed, paraffin-embedded tumor blocks from primary breast ductal carcinomas in 203 African-American females. Two separate 1mm cores represented each case. Tumors were subtyped based on expression of ER, PR, HER2, vimentin and 34βE12. Immunohistochemical evaluation for Claudin-4 was performed using rabbit monoclonal antibody (3E2C1, Invitrogen, 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. Claudin-4 expression was scored as low (H-score <100), moderate (H-score 100-199) and high (H-score >200). Bivariate analysis was done via χ2 analysis and multivariate analysis was done via Cox's proportional hazards model. Statistical significance was assumed if P < 0.05.
Results: Among our study population, 43.8% were Luminal A, 14.4% Luminal B, 8.5% HER2 +, and 33.3% triple negative of which 51% were basal-like phenotype. High claudin-4 expression was associated with high grade (p=0.0045), ER negativity (p=0.025), HER2 positivity (p<0.0001) and triple negative breast cancer (p<0.0001). Claudin expression was not associated with age size, PR, stage, or survival. 70% of triple negative cancers having basal-like phenotype showed high claudin-4 expression.
Conclusions: In our study, triple negative breast cancers in African-American women were associated with high claudin-4 expression. High claudin-4 was also associated with HER2+ and ER- cases. These markers may be useful in predicting progression and a poorer outcome in triple negative breast cancers which are more commonly found in African-American females. In our study, claudin-4 was also overexpressed in HER2+ breast cancers, which are also associated with poor outcome.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 11, Tuesday Morning