Up-regulation of Neutrophil Gelatinase-Associated Lipocalin in Esophageal Squamous Cell Carcinoma: Significantly Correlated with Cell Differentiation and Tumor Invasion

Abstract

Background and aims: Neutrophil-gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family. Elevated NGAL expression was reported in several types of cancers recently. However, the characteristics of NGAL expression in ESCC are still unknown. The aim of this study is to demonstrate the roles of NGAL in ESCC.

Methods: NGAL expression in 81 paraffin sections, including ESCC, normal mucosa, simple hyperplasia, dysplasia, and 73 fresh specimens of ESCC were analyzed by immunohistochemistry, western blot and gelatin zymography.

Results: In immunohistochemical study, ESCC showed a diverse staining pattern for NGAL. However, only weak positive signal was present within restricted cytoplasmic area in normal esophageal epithelium. In the dysplasia, altered NGAL expression could also be observed. In western blot study, NGAL expression level was significantly higher in ESCC than that in normal mucosa (P=0.030) and positively correlated with cell differentiation. However, no significant association was observed between NGAL expression and cell proliferation. In addition, the enzymic activity of NGAL/MMP-9 complex was much higher in ESCC than that in normal mucosa and significantly correlated with the depth of tumor invasion in zymography analysis (P=0.006).

Conclusions: Our findings suggested that NGAL was involved in the differentiation pathway and invasive progression of ESCC.