Correlation Between MMP1-PAR1 Axis and Clinical Outcome of Primary Gallbladder Carcinoma

Objective: Matrix metalloprotease-1 and protease-activated receptor-1 axis plays an important role in many cancers, with activation often associated with poor survival. The aim of the present study was to determine whether the immunohistochemical detection of matrix metalloprotease-1 and protease-activated receptor-1 could provide useful information as novel therapeutic or prognostic factors in primary gallbladder carcinoma. Methods: Eighty-six gallbladder carcinoma tissues were evaluated by immunohistochemistry for matrix metalloprotease-1 and protease-activated receptor-1 expressions. The association of matrix metalloprotease-1 and protease-activated receptor-1 expressions with clinicopathological characteristics and the univariate survival analysis for the influence of matrix metalloprotease- 1 and protease-activated receptor-1 expressions on the overall survival were analyzed. Results: Matrix metalloprotease-1 and protease-activated receptor-1 immunoreactivities were observed in 62 (72.1%) and 59 (68.6%) of the 86 gallbladder carcinoma cases, respectively. The tumors with the positive expressions of matrix metalloprotease-1 (P = 0.007) and protease-activated receptor-1 (P = 0.01) more frequently showed lymph node metastasis, respectively. In addition, the tumors with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 tended to show a deeper invasion depth (P = 0.006 and 0.008, respectively) and more frequent lymphovascular invasion (both P = 0.01). The Kaplan-Meier survival curves demonstrated that patients with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 had a significantly shorter survival time than those patients with their negative expression (both P = 0.02). Conclusions: A subset of gallbladder carcinoma cases revealed the overexpression of matrix metalloprotease-1 and protease-activated receptor-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, matrix metalloprotease- 1 and protease-activated receptor-1 expressions may be predictors for a poor prognosis in patients with gallbladder carcinoma. This is the first report describing about the involvement of matrix metalloprotease-1 and protease-activated receptor-1 axis in gallbladder carcinoma.