title: Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer.
abstract: Neutrophil gelatinase-associated lipocalin (NGAL) is a small, secreted glycoprotein with proposed functions in cell proliferation, survival and morphogenesis. NGAL is expressed in a variety of tumor types including breast carcinomas, but it is not known whether NGAL contributes directly to breast cancer progression. This study examines the relationship between NGAL expression in breast carcinomas and established clinical prognostic markers as well as clinical outcome. Using immunohistochemistry in tissue microarrays containing well characterized tumor samples from 207 breast cancer patients, NGAL was detected in 68 breast carcinomas in a cytoplasmic location. NGAL expression correlated strongly with negative steroid receptor status, HER-2/neu overexpression, poor histologic grade, the presence of lymph node metastases and a high Ki-67 proliferation index. In univariate survival analysis, NGAL expression was associated with decreased disease-specific survival and decreased disease-free survival in the entire cohort. In multivariate analysis, NGAL remained an independent prognostic marker for disease-free survival. In a subset of patients with estrogen receptor positive tumors, NGAL was significantly associated with decreased disease-free survival. The results show that NGAL expression is a predictor of poor prognosis in primary human breast cancer and suggest that NGAL detection may provide information for risk assessment and identify a subset of patients requiring more aggressive adjuvant therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Clinical Sciences Center K4/812, Madison, WI 53792-8550, USA.
authors.forename: Maret
authors.initials: M
authors.lastname: Bauer
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.forename: Michael N
authors.initials: MN
authors.lastname: Gould
authors.forename: Christoph
authors.initials: C
authors.lastname: Mundhenke
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.forename: Andreas
authors.initials: A
authors.lastname: Friedl
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins