PROGNOSTIC RELEVANCE OF MMP-2 (72-KD COLLAGENASE-IV) IN GASTRIC-CANCER

The association of MMP-2 (matrix metalloproteinase 2, 72-kD collagenas e IV) with invasive and metastatic capacity of tumor cells has implica ted a potential role in the prognosis for cancer patients. However, no larger study has been done to prove this hypothesis. The present stud y was therefore designed to investigate the prognostic impact of MMP-2 in a prospective series of 203 gastric cancer patients. MMP-2 express ion was measured immunohistochemically and scored semiquantitatively ( score 0-3) in carcinoma cells, and results were correlated with clinic opathological tumor parameters and parameters of the urokinase-type pl asminogen activator (uPA) system. Survival analyses were done using th e Kaplan-Meier method (log-rank statistics) and multivariate Cox analy sis. Significant correlations were found for MMP-2 and Lauren's classi fication, M stage and proteases/inhibitors of the uPA system in the pr imary tumor. Kaplan-Meier analysis revealed an association of increasi ng MMP-2 expression with worse prognosis. This was especially seen in patients with a parallel high expression of uPA receptor. However, dif ferences in survival probabilities between low and high MMP-2 levels w ere not significant. In a separate analysis of diffuse-type cancers, M MP-2 was significantly associated with disease-free (p = 0.0056) and o verall survival (p = 0.0426). Multivariately, MMP-2 was not an indepen dent parameter. Our results demonstrate that there is an association o f immunohistochemical detection of MMP-2 with prognosis of cancer pati ents. For diffuse gastric cancers, it is a significant prognostic para meter, however, not of independent impact. The study further suggests that consideration of interrelated tumor-associated proteases like uPA receptor in combination with MMP-2 may improve its prognostic power.