Matrix metalloproteinases (MMP) play an important role in tumor cell invasi
on and metastasis. We examined the expression of MMPs in hepatocellular car
cinoma (HCC) to determine whether they may help indicate the progression of
HCC and patient outcome. The expression of MMP-1, -2, -7, -9, and MT1-MMP
were determined in 37 pails of HCC and adjacent non-tumor tissue specimens
by semiquantitative reverse transcription polymerase chain reaction (RT-PCR
). The tumor to non-tumor (T/N) ratios for mRNA expression of each MMP were
compared with the clinicopathological findings and two-year disease-free s
urvival rates. Immunohistochemical analysis for MMP-1 and -9 was performed
in 30 specimens. MMP-1 and -9 expression was significantly higher in tumor
tissue than in non-tumor tissue (p=0.001 and 0.0078, respectively). By cont
rast, the expression of MMP-2 and -7 was significantly lower in tumor tissu
e than in non-tumor tissue (p=0.003 and 0.03, respectively). A higher MMP-9
TIN ratio was significantly associated with small HCCs (less than or equal
to 2 cm) and higher serum AFP values (greater than or equal to 20 ng/ml) (
p=0.013 and 0.028, respectively). Immunohistochemical analysis suggested th
at well differentiated HCC showed stronger immunoreactivity for MMP-9 than
moderately differentiated HCC. MMP T/N ratio was not significantly associat
ed with the disease-free survival rates. Overexpression of MMP-9 mRNA (T/N
ratio greater than or equal to 2) may be associated with the progression of
small HCC (less than or equal to 2 cm).