Matrix metalloproteinase-7 expression and biologic aggressiveness of cholangiocellular carcinoma

Cancer. 2002 Jan 15;94(2):428-34. doi: 10.1002/cncr.10235.

Abstract

Background: Matrix metalloproteinase-7 (MMP-7) recently has been reported to play a role in tumor cell invasion. The objective of the current study was to examine the expression of MMP-7 in patients with cholangiocellular carcinoma.

Methods: Twenty-six patients underwent resection of cholangiocellular carcinoma, leaving no macroscopic evidence of residual tumor. Immunostaining was performed to evaluate the relation between MMP-7 expression and clinicopathologic features and patient prognosis. The immunostaining pattern of the tumor cells for MMP-7 was classified as negative (-) (n = 9), positive (+) (n = 11), or strongly positive (++) (n = 6). Western blot analysis was performed to investigate the expression of active or latent forms in cancerous and noncancerous lesions in four patients.

Results: The survival rates in patients with MMP-7 expression judged to be (-), (+), and (++) were 75%, 80%, and 0%, respectively, at 1 year, and 47%, 24%, and 0%, respectively, at 3 years. The survival rate of MMP-7 (++) patients was significantly lower than that of MMP-7 (+) patients (P = 0.003) and MMP (-) patients (P = 0.008). At last follow-up, 3 patients in the MMP-7 (-) group had survived for > 5 years. Western blot analysis demonstrated that there were two types of cholangiocellular carcinoma: those producing both latent and active MMP-7 and those producing only the latent form.

Conclusions: Although the results of the current study are based on a small number of patients, they suggest that MMP-7 expression is a significant prognostic factor in patients with cholangiocellular carcinoma and that cholangiocellular carcinoma demonstrating strongly positive expression of MMP-7 on immunostaining may have a higher malignant potential compared with that showing negative or positive expression of MMP-7.

MeSH terms

  • Bile Duct Neoplasms / enzymology*
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / enzymology*
  • Bile Ducts, Intrahepatic / pathology
  • Blotting, Western
  • Cholangiocarcinoma / enzymology*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology
  • Female
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 7 / metabolism*
  • Neoplasm Invasiveness
  • Prognosis
  • Survival Rate

Substances

  • Matrix Metalloproteinase 7