MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer.
OBJECTIVE
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.


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.
Mrena
J
J
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Wiksten
J-P
JP
Nordling
S
S
Kokkola
A
A
Ristimäki
A
A
Haglund
C
C
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D017677:Age Distribution; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9