AUGMENTED MEMBRANE TYPE-1 MATRIX METALLOPROTEINASE (MT1-MMP) MMP-2 MESSENGER-RNA RATIO IN GASTRIC CARCINOMAS WITH POOR-PROGNOSIS/

The activation of zymogen and the amount of proteinase and its inhibit ion are important in determining the eventual activity of matrix-degra ding enzymes involved in tumor aggressiveness. To evaluate a gene comp lement leading to matrix metalloproteinase 2 (MMP-2; M-r 72,000 gelati nase) activity, membrane type I MMP (MT1-MMP), urokinase-type plasmino gen activator, MMP-2, and tissue inhibitor of metalloproteinase 2 tran scriptional levels were measured in gastric carcinoma biopsies, Compar ative tumor:normal tissue reverse transcription-PCR in a cohort of 25 patients revealed up to a 10-fold difference in the expression of MT1- MMP, a metalloproteinase that has been proposed as a membrane receptor activator of MMP-2; a 1-unit increment resulted in a 30% risk to surv ival. A 20% risk also resulted from a 1-unit increment in the MT1-MMP: MMP-2 ratio, which showed differences of up to 15-fold. instead, the expression of urokinase-type plasminogen activator, which trips off a cascade ending in the activation of MMP-2, as well as the expression o f MMP-2 itself and its inhibitor, tissue inhibitor of metalloproteinas e 2, lacked correlation with patient follow-up. Zymography revealed MM P-2 activities that were often in conflict with the transcription resu lts and also with follow-up. The results suggest the evaluation of MT1 -MMP and/or MT1-MMP:MMP-2 transcription as a new preoperative molecula r-level prognostic factor for gastric carcinoma.