Lipocalin-2/NGAL Expression Is Associated with Clinical Outcome in Invasive Mammary Carcinoma
EA Slodkowska, D Cho, AB Boguniewicz, CB Sheehan, CE Sheehan, JS Ross. Albany Medical College, Albany, NY
Background: Lipocalin-2 functions as a transporter of small lipophilic ligands and has been shown to induce the epithelial to mesenchymal transition and tumor invasion in experimental breast cancer models.
Design: Formalin-fixed, paraffin-embedded tissue sections from 146 cases of invasive mammary carcinoma (102 ductal carcinomas (IDC) and 44 lobular carcinomas (ILC) were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using rat monoclonal lipocalin-2/NGAL (R&D Systems, Minneapolis, MN). Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: Weak cytoplasmic staining of benign breast epithelium was identified in 100% of cases. Intense cytoplasmic lipocalin-2 overexpression was observed in 78/146 (53%) of invasive carcinomas. Lipocalin-2 overexpression correlated with PR positive status overall [63% PR positive versus 41% PR negative, p=0.012], within the IDC subgroup [63% PR positive versus 35% PR negative, p=0.009], and within the ER negative subgroup [80% PR positive versus 32% PR negative, p=0.007]; disease recurrence overall [69% recurrent versus 48% non-recurrent, p=0.021], within the IDC subgroup [70% recurrent versus 42% non-recurrent, p=0.011], and within the ER negative subgroup [72% recurrent versus 29% non-recurrent, p=0.004]; while the subgroup of positive tumors exhibiting intense diffuse lipocalin-2 overexpression 54/146 (37%) correlated with shortened survival within the ER negative subgroup [42% expired versus 15% alive, p=0.046] and the converse within the ER positive subgroup [32% expired versus 55% alive, p=0.027]. There was no correlation between lipocalin-2 expression and HER2 status (FISH). On multivariate analysis, advanced stage, lipocalin-2 overexpression, ER negative status, metastatic disease at diagnosis and positive node status were independent predictors of disease recurrence; while advanced stage, metastatic disease at diagnosis and positive node status were independent predictors of shortened survival.
Conclusions: Lipocalin-2 overexpression in invasive mammary carcinoma is significantly associated with hormone receptor status and independently predicts disease recurrence after primary treatment. Further study of this biomarker in breast cancer patients appears warranted.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 36, Monday Morning