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MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer
  1. J Mrena1,
  2. J-P Wiksten1,
  3. S Nordling2,3,
  4. A Kokkola1,
  5. A Ristimäki2,4,*,
  6. C Haglund1,2,*
  1. 1Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
  2. 2Department of Pathology, Helsinki University Central Hospital
  3. 3Haartman Institute, Biomedicum Helsinki, University of Helsinki, Helsinki
  4. 4Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki
  1. Correspondence to:
    Dr Caj Haglund
    Department of Surgery, Helsinki University Central Hospital, PO Box 340, 00029 HUS, Helsinki, Finland; caj.haglund{at}


Background and aim: Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. As cyclo-oxygenase-2 (COX-2) has been shown to activate MMPs, creating one of the COX-2-promoted pathways of tumour growth and metastasis, the prognostic role of MMP-2 and MMP-9 in gastric cancer was assessed and their association with COX-2 expression was evaluated.

Materials and methods: Samples were collected from 342 consecutive patients operated on for gastric cancer, of which 315 were acceptable for MMP-2, MMP-9 and COX-2 immunohistochemistry. Specimens were stained with specific antibodies, evaluated and categorised by two interpreters, and then correlated with clinical data and survival.

Results: Epithelial MMP-2 immunoreactivity was associated with male sex, high stage, advanced penetration depth, non-curative surgery, high COX-2 expression and poor survival. Stromal MMP-2 expression correlated with high stage, intestinal type and non-curative surgery whereas MMP-9 correlated only with intestinal type. Stage, intent of surgery and COX-2 were independent prognostic factors.

Conclusions: Epithelial MMP-2 expression in gastric cancer is associated with aggressive forms, COX-2 and poor survival, although MMP-2 was not an independent prognostic factor. In gastric cancer tumour growth is apparently induced by COX-2, and invasion is mediated by MMP-2.

  • COX-2, cyclo-oxygenase-2
  • MMP, matrix metalloproteinase

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  • * These authors contributed equally.