Messenger RNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human hepatocellular carcinoma.

BACKGROUND

The prognosis of patients with hepatocellular carcinoma is relatively poor because of the high rate of intrahepatic recurrences. We have previously demonstrated an association between enhanced secretion of active matrix metalloproteinases (MMPs; gelatinase A and matrilysin) and early recurrence in hepatocellular carcinoma. The aim of this study was to examine further the relationship between messenger RNA levels of metalloproteinases and their inhibitors and behavior of this carcinoma.

METHODS

Messenger RNA expression of gelatinase A, gelatinase B, matrilysin and tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 were analyzed in 30 patients with hepatocellular carcinoma by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The results were contrasted with the clinicopathological data of the patients.

RESULTS

Enhanced mRNA expression of gelatinase A, gelatinase B and matrilysin in tumor was observed in 20, 22 and 19 of 30 patients, respectively. Enhanced mRNA expression of gelatinase A or gelatinase B and of matrilysin showed trends toward presence of capsular invasion (P = 0.078) and intrahepatic metastasis (P = 0.064), respectively. Concomitant overexpression of gelatinase A and matrilysin was associated with portal invasion, intrahepatic metastasis and recurrence within the first postoperative year (P < 0.05). A modest increase of mRNA expression of TIMP-1 and TIMP-2 in tumor was observed in half of the patients, but did not correlate with any clinicopathological features.

CONCLUSION

Our results suggest that semiquantitative RT-PCR analysis of MMPs may be helpful in disease management of patients with hepatocellular carcinoma.