Expression of MMP-2,TIMP-2 protein and the ratio of MMP-2/TIMP-2 in gallbladder carcinoma and their significance.

Abstract

To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinical-pathological parameters of patients with gallbladder carcinoma. Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinical-pathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded. There was significant difference between the average level (1.123+/-0.108 vs 1.030+/-0.054, P=0.002) of MMP-2, the ratio (1.050+/-0.013 vs 0.937+/-0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, significant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168+/-0.067 vs 1.048+/-0.075, 1.170+/-0.062 vs 1.039+/-0.069, 1.039+/-0.076 vs 1.147+/-0.083, 1.048+/-0.074 vs 1.103+/-0.095, P<0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder. TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in the judgment of invasion or metastasis and the estimate of prognosis in patients with gallbladder carcinomas.