Prognostic impact of tissue inhibitor of matrix metalloproteinase-1 in esophageal carcinoma

Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the activity of m atrix metalloproteinase, which may play an important role in carcinoma inva sion and metastasis. TIMP-1 is thus considered to inhibit carcinoma invasio n and metastasis. However, TIMP-1 possesses another important function, cel l growth promotion. The clinical significance of TIMP-1 expression has not been fully determined in esophageal carcinoma. We thus examined the express ion of TIMP-1 mRNA in tumor (T) and corresponding normal (N) tissues of 85 esophageal carcinoma cases by RT-PCR. The T:N ratio of TIMP-1 mRNA expressi on in each case was evaluated semiquantitatively with adjustment by an inte rnal control gene. The mean T:N ratio was 2.0 (range 0.2-6.5). When compari ng high-expression cases (T:N > 2.0, n = 37) with low-expression cases (T:N less than or equal to 2.0, n = 48), the former showed a significantly high er frequency of lymph vessel invasion, vascular vessel invasion, lymph node metastasis and advanced-stage disease. The former cases showed a poorer pr ognosis than the latter. Multivariate analysis disclosed that TIMP-1 expres sion status was an independent determining factor for prognosis. Our findin gs suggest that TIMP-1 expression correlates with tumor extension of esopha geal carcinoma and might, if validated, prove useful as a novel prognostic marker for esophageal carcinoma. (C) 2000 Wiley-Liss, Inc.