Prognostic significance of MMP-9 and TIMP-1 in liver metastases

Rom J Morphol Embryol. 2015;56(2):357-64.

Abstract

Our research focuses both on the correlations between MMP-9 and TIMP-1 and classical clinicopathological factors and on the prognostic value of MMP-9 and TIMP-1 for survival. The study group included 52 patients diagnosed with hepatic metastases. The tissue specimens have been specifically processed for immunohistochemical exam, by using anti-MMP-9 and anti-TIMP-1 antibodies. For the semi-quantitative assessment, we have used an individualized score, which values allowed the discrimination of two classes of cases (low and high), using two different thresholds: ≤4 and <4. Data have been statistically analyzed by using Fisher 2×2 test and Kaplan-Meier curves. Statistical analysis between MMP-9 and TIMP-1 expression (low versus high, separately for each threshold) and clinicopathological characteristics had not revealed significant differences. In both types of threshold applied in survival analysis, significant differences between MMP-9 and TIMP-1 low and high expression have been demonstrated. For cases with concordant MMP-9-TIMP1 co-expression, low versus high, the survival analysis revealed that threshold value <4 offers a better stratification of cases when compared to threshold value ≤4, based on significant differences registered only for threshold value <4. No significant differences were registered between cases with discordant MMP-9-TIMP-1 co-expression, for both thresholds. Regardless of the used threshold, the survival analysis achieved between the cases with MMP-9-TIMP-1 concordant co-expression and cases with MMP-9-TIMP-1 discordant co-expression had proven significant differences. Our study suggests that the confirmation of MMP-9 and TIMP-1 value as prognostic factors, based on immunohistochemical expression, requires a threshold validation.

MeSH terms

  • Aged
  • Female
  • Humans
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / secondary*
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Prognosis
  • Survival Analysis
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*

Substances

  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9