Immunocytochemical detection of MMP-3 and-10 expression in hepatocellular carcinomas

Structural changes in the extracellular matrix (ECM) are necessary for cell migration doping tissue remodeling and tumor invasion. The matrix metallop roteinases (MMPs) and their inhibitors have been shown to be critical modul ators of ECM composition and are thus crucial in neoplastic cell invasion a nd metastasis. Expression of MMP-2, -3, -9, -10, and 13 was investigated in human hepatocellular carcinomas (HCCs) employing an indirect alkaline phos phatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells/surroundin g stroma that reacted positively and (b) a measure of staining intensity [g raded-from A (highest) to D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall e xpression of MMP-3 and -10 was found in HCCs, especially in the ECM adjacen t to blood vessels. Positive immunoreactivity could be seen for these two M MPs in the ECM surrounding over 90% of the neoplastically transformed cells (++++), and the staining intensity was also the strongest possible (A,B). No immunoreactivity was detected using antibodies directed against MMP-2, 9 , and -13.