Lipocalin 2 expression is associated with aggressive features of endometrial cancer

Abstract

BackgroundIncreased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival.MethodsImmunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies.ResultsExpression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage.ConclusionIncreased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.

An early-screening biomarker of endometrial carcinoma: NGAL is associated with epithelio-mesenchymal transition

“…These results are in accordance with Miyamoto's first report of NGAL in EC [30, 31]. The present study verified a significantly increased NGAL expression in early-grade Ishikawa EC cell line when compared to high-grade HEC-1A and KLE cell lines, suggesting it may serve as a biomarker for early-stage screening for EC.…”

Comparative Analysis of Iron Metabolism and Its Adjustment Changes at Cancer Patients in Childhood

“…In human cancer tissues, expression of elevated levels of LCN-2, which plays a role in the intracellular transport of iron, has been detected in breast, ovarian, endometrial, intestinal, lung, pancreatic, oesophageal and gastric cancers (13)(14)(15)(16)(17)(18). In our study, levels of LCN-2 were found significantly high (P = 0.001) in all patient groups at diagnosis.…”

Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome

“…It is able to transport small lipophilic ligands, such as lipopolysaccharides (Bratt et al 1999), through the hydrophilic body fluid and acts as a bacteriostatic protein. LCN2 was first isolated from human neutrophils and has now been found to be expressed in several types of cells, including adipocytes (Zhang et al 2008), macrophages (Zhang et al 2008), brain endothelial cells (Hamzic et al 2012), hepatocytes (Jayaraman et al 2005), endometrial carcinoma cells (Mannelqvist et al 2012), and erythroid progenitor cells (Miharada et al 2005).…”