title: Stromal expression of neutrophil gelatinase-associated lipocalin correlates with poor differentiation and adverse prognosis in oral squamous cell carcinoma.
abstract: OBJECTIVE
  Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily. Although its overexpression in various cancers has been reported, little is known about its expression and clinical significance in oral squamous cell carcinoma (OSCC). This study aimed to elucidate the clinical significance of NGAL in OSCC.
  
  
  RESULTS
  We investigated NGAL expression immunohistochemically in tumour cells and stromal cells in 96 OSCC tissues. NGAL expression in tumour cells correlated significantly with histological tumour cell differentiation, as shown by its specific distribution in the horn pearl-forming keratinized tumour cells, but not with other major clinicopathological parameters. We found NGAL(+) cells in the stroma that were predominantly myeloperoxidase-positive neutrophils. The number of such NGAL-expressing stromal cells was associated significantly with poor differentiation and reduced overall survival in OSCC. The prognostic value of stromal NGAL expression was significant in a univariate analysis, while only a trend was found in multivariate analyses.
  
  
  CONCLUSIONS
  This study is the first to show the clinical significance of stromal NGAL expression, which may be an indicator of poor prognosis and more aggressive histological grade in OSCC. Our data suggest that NGAL expression in tumour cells and expression in stroma are associated in different ways with OSCC differentiation.
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinriki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Ota
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ota
authors.forename: Takanao
authors.initials: T
authors.lastname: Sueyoshi
authors.forename: Jianying
authors.initials: J
authors.lastname: Guo
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hayashi
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Hiraki
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Masanori
authors.initials: M
authors.lastname: Shinohara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
keywords: neutrophil gelatinase-associated lipocalin; oral squamous cell carcinoma; tumour cell differentiation