Differential expression of matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in hepatocellular and pancreatic adenocarcinoma: Implications for tumor progression and clinical prognosis

In the present study, we used in situ hybridization to study 36 primary hep atocellular carcinomas (HCCs) and 35 pancreatic adenocarcinomas to analyze the expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP- 2, and MMP-9 mRNAs, In HCCs, MT1-MMP mRNA was mainly expressed by cancer ce lls and to a lesser extent by stromal cells. MMP-2 mRNA was expressed predo minantly by cells of tumor stroma, whereas MMP-9 mRNA was seen mainly in ne oplastic epithelial cells. In pancreatic adenocarcinomas, MT1-MMP and MMP-9 mRNA were seen at moderate levels both in cancer and in stromal cells, whe reas MMP-2 mRNA was predominantly expressed by the tumor stroma, Antigens o f MMP-2, MMP-9, and MT1-MMP immunolocalized to the neoplastic epithelium an d to the stromal cells in both tumor types. In gelatin zymography, increase d amounts of latent and active MMP-2 were found in tumor samples of HCC as compared with adjacent nontumorous liver tissue. On the other hand, the lat ent form of MMP-9 was found in almost equal amounts both in tumor and norma l liver samples, but its active form was present only in HCC. Expression of MT1-MMP mRNA had a tendency to be associated with a lower deg ree of differentiation in HCC, but such association was not noticed in panc reatic tumors. Correlation to the clinical data showed that MT1-MMP express ion had a strong statistical association with a poor outcome of patients (P < 0,01), A similar tendency was also observed in pancreatic adenocarcinoma s, but the association did not reach statistical significance. MMP-2 and MM P-9 mRNA expression did not have significant correlation with prognosis. Th e results of this study support the previous suggestions of the importance of MT1-MMP for malignant growth and indicate that increased MT1-MMP mRNA ex pression by tumor cells in HCCs and pancreatic adenocarcinomas may have pro gnostic significance.