title: Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression: a marker of malignant potential?
abstract: BACKGROUND
  Neutrophil gelatinase-associated lipocalin (NGAL) has a diverse functional repertoire, involved in the innate immune response as well as cell growth and differentiation. Expression has been linked to malignant disease development and progression.
  
  
  METHODS
  Neutrophil gelatinase-associated lipocalin expression was assessed immunohistochemically in 98 colorectal neoplastic lesions (52 cancer polyps (CaPs) and 46 sporadic adenoma/adjacent normal mucosa paired specimens) to investigate association with adenoma progression and early colorectal carcinogenesis.
  
  
  RESULTS
  Within CaPs, all adenomatous and carcinomatous epithelium expressed NGAL, with 92% (43 out of 47) and 58% (19 out of 33) epithelial positivity, respectively, as well as positive stromal cell expression. This was significantly increased compared with normal mucosal epithelium (P=0.0001). Neutrophil gelatinase-associated lipocalin positivity was also identified in sporadic low-grade adenomas, in both the epithelial and stromal compartments as compared with adjacent normal mucosa (P=0.0001 and 0.0002), and this increased along with adenoma size >1 cm (P=0.03).
  
  
  CONCLUSIONS
  Neutrophil gelatinase-associated lipocalin is expressed by the majority of human neoplastic colorectal lesions. This phenotypic switch occurs at an early stage in neoplastic progression with clear differential expression between normal mucosa and adenomatous polyps, rather than further downstream in disease progression at the adenoma-carcinoma transformation. Thus, NGAL expression is not a useful biomarker for determining disease progression from adenomatous to malignant colorectal neoplasia.
authors.affiliation: Gastrointestinal Research Group, Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. m.h.mclean@abdn.ac.uk
authors.forename: M H
authors.initials: MH
authors.lastname: McLean
authors.forename: A J
authors.initials: AJ
authors.lastname: Thomson
authors.forename: G I
authors.initials: GI
authors.lastname: Murray
authors.forename: N
authors.initials: N
authors.lastname: Fyfe
authors.forename: G L
authors.initials: GL
authors.lastname: Hold
authors.forename: E M
authors.initials: EM
authors.lastname: El-Omar
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins