Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer

被引:201
作者
Bauer, Maret [1 ]
Eickhoff, Jens C. [2 ]
Gould, Michael N. [3 ]
Mundhenke, Christoph [4 ]
Maass, Nicolai [4 ]
Friedl, Andreas [1 ]
机构
[1] Univ Wisconsin, Dept Pathol & Lab Med, Ctr Clin Sci, Madison, WI 53792 USA
[2] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USA
[3] Univ Wisconsin, Dept Oncol, Madison, WI 53792 USA
[4] Univ Hosp Schleswig Holstein, Dept Gynecol & Obstet, Kiel, Germany
关键词
breast cancer; lipocalins; metalloproteinase; NGAL; prognostic marker;
D O I
10.1007/s10549-007-9619-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:389 / 397
页数:9
相关论文
共 40 条
  • [1] Altman DG., 1990, PRACTICAL STAT MED R
  • [2] STUDIES OF THE RELEASE AND TURNOVER OF A HUMAN NEUTROPHIL LIPOCALIN
    AXELSSON, L
    BERGENFELDT, M
    OHLSSON, K
    [J]. SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION, 1995, 55 (07) : 577 - 588
  • [3] Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype
    Baba, Fusun
    Swartz, Kathryn
    van Buren, Regina
    Eickhoff, Jens
    Zhang, Yong
    Wolberg, William
    Friedl, Andreas
    [J]. BREAST CANCER RESEARCH AND TREATMENT, 2006, 98 (01) : 91 - 98
  • [4] Iron chelators in cancer chemotherapy
    Buss, JL
    Greene, BT
    Turner, J
    Torti, FM
    Torti, SV
    [J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (15) : 1623 - 1635
  • [5] Ribonucleotide reductase, lipoxygenase and the intracellular low-molecular-weight iron pool
    Cooper, CE
    Porter, JB
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 1997, 25 (01) : 75 - 80
  • [6] Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans
    Cowland, JB
    Borregaard, N
    [J]. GENOMICS, 1997, 45 (01) : 17 - 23
  • [7] Neutrophil gelatinise-associated lipocalin is up-regulated in human epithelial cells by IL-1β, but not by TNF-α
    Cowland, JB
    Sorensen, OE
    Sehested, M
    Borregaard, N
    [J]. JOURNAL OF IMMUNOLOGY, 2003, 171 (12) : 6630 - 6639
  • [8] The matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin complex plays a role in breast tumor growth and is present in the urine of breast cancer patients
    Fernández, CA
    Yan, L
    Lous, G
    Yang, J
    Kutok, JL
    Moses, MA
    [J]. CLINICAL CANCER RESEARCH, 2005, 11 (15) : 5390 - 5395
  • [9] Flower DR, 1996, BIOCHEM J, V318, P1
  • [10] Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues. Cell type-specific pattern of expression
    Friedl, A
    Stoesz, SP
    Buckley, P
    Gould, MN
    [J]. HISTOCHEMICAL JOURNAL, 1999, 31 (07): : 433 - 441