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Expression of matrix metalloproteinase-1 and membrane type-1 matrix metalloproteinase in human primary gallbladder carcinomas withvasculogenic mimicry and its clinical significance
FAN Yue-zu,SUN Wei,ZHANG Wen-zhong,GE Chun-yan
2014, 3 (1):
8-16.
Objective To evaluate the expression of matrix metalloproteinase-1(MMP-1) and membrane type-1 matrix metalloproteinase (MT1-MMP) in human primary gallbladder carcinomas with vasculogenic mimicry (VM) and its clinical significance.Methods Seventy-four carcinomas,10 adenomas and 10 chronic inflammatory lesions of the gallbladder underwent operation and confirmed histopathologically and their clinical-pathlogical data were studied and followedup.Immunohistochemistry (SABC) was used to determine the expression of MMP-1,MT1-MMP proteins in each paraffin section of every patient in vivo.Kaplan-Meier survival curves and Cox multiple factor were used to analyse the relation beteewn VM of gallbladder carcinomas and expression of MMP-1,MT1-MMP.Results ① Expression of MMP-1 and MT1-MMP was increased significantly in carcinomas with or without VM than adenomas and inflammatory lesions of the gallbladder (P<0.000 1) in.Eexpression of MT1-MMP in the gallbladder carcinomas with VM was increased significantly than that without VM (P=0.003 9),without difference on expression of MMP-1 between VM (+) gallbladder carcinomas and VM (-) gallbladder carcinomas.② There is positive correlation between expression of MMP-1 and VM (-) gallbladder carcinomas in the cases of Nevin stage (P=0.003 6),differentiation degree (P=0.010),liver metastatis (P=0.003) and lymph node metastases (P=0.002),the same correlation was observed between expression of MT1-MMP and VM (+)/(-) gallbladder carcinomas in the cases of Nevin stage (P=0.013 or P=0.003 3),invasion depth (P=0.045 or P=0.035),lymph node metastases (P=0.046 or P=0.025) and liver metastatis (P=0.030 or P=0.027); MMP-1 expression was positively correlated with MT1-MMP expression in VM (-) gallbladder carcinomas.③ Expression of MT1-MMP in the same conditions of Nevin stage (S3~S5,P=0.000 1),serosal invasion (P=0.001),lymph node metastases (P=0.000 2),liver metastatis (P=0.004) was higher significantly in VM (+) gallbladder carcinomas than VM (-) gallbladder carcinomas; Furthermore,expression of MMP-1 in the cases of liver metastatis (P=0.0038) was higher significantly in VM (+) gallbladder carcinomas than VM (-) gallbladder carcinomas.④ VM (+) gallbladder carcinoma group underwent operation with positive expression of MMP-1 and MT1-MMP had shorter 5-year survival than the respectively VM (-) group (P=0.025 1; P=0.022 5),the same correlation was observed in positive coexpression of MMP-1 and MT1-MMP (P=0.025 0).Cox analysis showed that VM,invasion depth,lymph node metastasis,hepatic metastasis,and operation method were independent risk factors of the prognosis of patients with primary gallbladder carcinoma.Conclusions Higher expression of MMP-1,MT1-MMP in gallbladder carcinomas,a positive correlation between expression of MT1-MMP and VM of gallbladder carcinomas and no correlation between expression of MMP-1 and VM of gallbladder carcinomas were observed.MMP-1 and MT1-MMP are important clinical markers for staging of Nevin stage,judgement of invasion depth,lymph node or liver metastatis,and evaluation of prognosis in patients with gallbladder carcinoma.MT1-MMP may be especially of important for evaluating if there is VM in human gallbladder carcinomas and prognosis of patients with VM (+) gallbladder carcinoma.
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