Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) prognostic value in stage I colorectal carcinoma

Pathol Res Pract. 2011 Aug 15;207(8):479-86. doi: 10.1016/j.prp.2011.05.012. Epub 2011 Jul 2.

Abstract

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to behave like a negative prognostic marker in stage I colorectal carcinoma. In the aim of clarifying whether its association with adverse outcome may descend from NGAL's ability to regulate matrix metallo-proteinase-9 (MMP-9), we analyzed the correlation, prognostic value, and association with neo-angiogenesis of NGAL and MMP-9 immunohistochemical expression in a series of stage I colorectal carcinomas. A variable NGAL immunoexpression was demonstrated in 17 of the 48 analyzed cases with a significantly higher frequency of positive cases among patients showing disease progression. NGAL expression was also positively correlated with VEGF expression detected in the same cases. MMP-9 immunostaining was present in the cytoplasm of the neoplastic cells in 30 cases; no significant correlations were evidenced with NGAL expression, as well as with the various clinico-pathological parameters or with progression of the colorectal carcinomas. By contrast, NGAL expression was confirmed as a significant independent negative prognostic marker related to a shorter disease-free survival in stage I colorectal carcinoma. Our preliminary results suggest that the association of NGAL with poor outcome might be independent from MMP-9 regulation, thus highlighting its prognostic value in this neoplasia. If our findings are confirmed in further analyses, NGAL assessment might be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis*
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lipocalin-2
  • Lipocalins / biosynthesis*
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • Proto-Oncogene Proteins / biosynthesis*

Substances

  • Acute-Phase Proteins
  • Biomarkers, Tumor
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Matrix Metalloproteinase 9