Expressions of Matrix Metalloproteinases-9 and Tissue Inhibitor of Metalloproteinase-1 in Pituitary Adenomas and Their Relationships with Prognosis

Cancer Biother Radiopharm. 2019 Feb;34(1):1-6. doi: 10.1089/cbr.2018.2589. Epub 2019 Jan 24.

Abstract

Objective: To investigate the expression levels of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in pituitary adenomas (PAs), and to analyze the relationship of the expressions of the two with the prognosis of patients.

Methods: A total of 108 patients with PAs diagnosed in our hospital from May 2010 to May 2012 were selected and divided into the invasive PA (IPA) group (n = 58) and the non-IPA group (n = 50) according to the invasiveness of PAs. Hematoxylin and eosin (H&E) staining was used to observe the pathological state of patients. The expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry and western blotting at protein level and reverse transcription-polymerase chain reaction at gene level, respectively. The expression levels of MMP-9 and TIMP-1 in serum of patients before operation were tested using enzyme-linked immunosorbent assay, and patients with PAs after operation were followed up.

Result: The positive expression rate of MMP-9 in IPAs was significantly higher than that in non-IPAs, whereas that of TIMP-1 was relatively high in non-IPAs, and the differences were statistically significant (p < 0.05). At both protein and gene levels, MMP-9 was highly expressed in IPAs, whereas TIMP-1 was highly expressed in non-IPAs, and the differences were statistically significant (p < 0.05 in all comparisons). Before operation, the expression level of MMP-9 in serum of patients with IPAs was relatively high, whereas that of TIMP-1 in serum of patients with non-IPAs was relatively high, and the differences were statistically significant (p < 0.05 in all comparisons).

Conclusion: The postoperative survival rate of patients with highly expressed MMP-9 was relatively low, whereas that of patients with highly expressed TIMP-1 was relatively high. The abnormal expressions of MMP-9 and TIMP-1 play important roles in the invasion process of PAs. The prognoses of patients with low expression MMP-9 and high expression TIMP-1 are more positive.

Keywords: matrix metalloproteinase-9; pituitary adenoma; prognosis; tissue inhibitor of metalloproteinase-1.

MeSH terms

  • Adenoma / enzymology*
  • Adenoma / pathology
  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Middle Aged
  • Pituitary Neoplasms / enzymology*
  • Pituitary Neoplasms / pathology
  • Prognosis
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*

Substances

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