Matrix metalloproteinase-7 expression and biologic aggressiveness of cholangiocellular carcinoma.
BACKGROUND
Matrix metalloproteinase-7 (MMP-7) recently has been reported to play a role in tumor cell invasion. The objective of the current study was to examine the expression of MMP-7 in patients with cholangiocellular carcinoma.


METHODS
Twenty-six patients underwent resection of cholangiocellular carcinoma, leaving no macroscopic evidence of residual tumor. Immunostaining was performed to evaluate the relation between MMP-7 expression and clinicopathologic features and patient prognosis. The immunostaining pattern of the tumor cells for MMP-7 was classified as negative (-) (n = 9), positive (+) (n = 11), or strongly positive (++) (n = 6). Western blot analysis was performed to investigate the expression of active or latent forms in cancerous and noncancerous lesions in four patients.


RESULTS
The survival rates in patients with MMP-7 expression judged to be (-), (+), and (++) were 75%, 80%, and 0%, respectively, at 1 year, and 47%, 24%, and 0%, respectively, at 3 years. The survival rate of MMP-7 (++) patients was significantly lower than that of MMP-7 (+) patients (P = 0.003) and MMP (-) patients (P = 0.008). At last follow-up, 3 patients in the MMP-7 (-) group had survived for > 5 years. Western blot analysis demonstrated that there were two types of cholangiocellular carcinoma: those producing both latent and active MMP-7 and those producing only the latent form.


CONCLUSIONS
Although the results of the current study are based on a small number of patients, they suggest that MMP-7 expression is a significant prognostic factor in patients with cholangiocellular carcinoma and that cholangiocellular carcinoma demonstrating strongly positive expression of MMP-7 on immunostaining may have a higher malignant potential compared with that showing negative or positive expression of MMP-7.
Miwa
Shiro
S
First Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan. smiwa@hsp.md.shinshu-u.ac.jp
Miyagawa
Shin-ichi
S
Soeda
Junpei
J
Kawasaki
Seiji
S
D001650:Bile Duct Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015996:Survival Rate
D020783:Matrix Metalloproteinase 7