Protein levels of tissue inhibitor of metalloproteinase-1 in tumor extracts as a marker for prognosis and recurrence in patients with gastric cancer.

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) correlates with tumor progression in patients with gastric cancer; however, the clinical significance of TIMP-1 as a marker for prognosis and recurrence has not been fully clarified.

Methods: TIMP-1 protein was measured by an enzyme-linked immunosorbent assay in tumor samples from 86 patients who had undergone surgical resection. An intratumoral TIMP-1 value of 10.0 ng/mg protein or more was defined as positive. Patients were followed up for more than 5 years prospectively.

Results: Thirty-one of the 86 patients (36.0%) were positive for TIMP-1. Kaplan-Meier curves for overall survival were significantly different between patients who were positive and those who were negative for TIMP-1. Univariate analysis of factors affecting overall survival showed that depth of tumor invasion; lymph node metastasis; peritoneal dissemination; lymphatic invasion; venous invasion; Lauren classification of histology; curability; and TIMP-1 were statistically significant. Stepwise multivariate analysis for overall survival demonstrated that depth of tumor invasion, nodal metastasis, peritoneal dissemination, and TIMP-1 remained independent prognostic factors. Kaplan-Meier curves for disease-free survival were significantly different between patients who were positive and those who were negative for TIMP-1. The incidence of recurrence was significantly higher in patients positive for TIMP-1 than in those who were negative for TIMP-1. The frequency at each site of recurrence was higher in patients positive for TIMP-1.

Conclusion: These results suggested that the protein concentration of TIMP-1 in the tumor extracts was a useful marker for overall survival, disease-free survival, and disease recurrence in patients with gastric cancer. Thus, tumor TIMP-1 may serve to identify a high-risk group, for whom optimal surgical and medical treatment can be given.