ANALYSIS OF MT1-MMP AND MMP2 EXPRESSION IN HUMAN GASTRIC CANCERS

Membrane-type I matrix metalloproteinase (MTI-MMP) is a presumed activ ator of MMP2, which is one of the major proteinases in tumor cell inva sion, in this study, we determined the clinico-pathologic significance of MTI-MMP expression in 68 human gastric carcinomas. The tumor-norma l ratio (TIN ratio) of MTI-MMP expression was determined by reverse tr anscription-polymerase chain reaction analysis. To visualize the local ization of MTI-MMP, an immunohistochemical study was performed. In add ition, a gelatin zymography was done to examine the activation ratio o f MMP2, and a correlation between MTI-MMP expression and activation of MMP2 was studied. The expression of MTI-MMP mRNA was higher in tumor tissue than in corresponding normal tissue in most cases. The mean val ue of the T/N ratio was 4.8. Twenty cases with T/N greater than or equ al to 4.8 showed significantly deeper invasion and higher frequency of lymph node metastasis than 48 cases with TIN < 4.8. MTI-MMP expressio n was an independent factor influencing both tumor invasion of the gas tric wall and lymph node metastasis. Although MTI-MMP expression was n ot an independent prognostic factor, the patients with T/N greater tha n or equal to 4.8 showed a significantly worse prognosis than those wi th T/N < 4.8. An immunohistochemical study demonstrated that MTI-MMP e xpression was mainly recognized in the tumor cells, There was a signif icant correlation between MTI-MMP expression and activation of MMP2. O ur findings suggest that: 1) the expression of MTI-MMP may influence p rognosis via tumor invasion of the gastric wall and lymph node metasta sis, and 2) MTI-MMP activation of MMP2. may be clinically relevant in gastric carcinoma tumors. (C) 1997 Wiley-Liss, Inc.