Recurrence or metastasis of HCC: predictors, early detection and experimental antiangiogenic therapy

Subject headings carcinoma, hepatocellular; neoplasm metasta sis; angiogenesis; liver neoplasms AIM To investigate the predictors for recurrence or metastas is of HCC, and to evaluate the effect of antiangiogenic therapy on the growth of transplantable human HCC in nude mice. METHODS RT-PCR was used to measure the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in 56 pairs of nontumorous liver and tumor samples. Sixty blood samples from human HCC were examined by nested RT-PCR to find out AFP mRNA. Recombinant human endostatin and polyclonal antibody against VEGF were administered to treat human HCC transplanted in nude mice. RESULTS Thirty of 56 HCC samples showed stronger expression of MMP-9 in tumorous tissues than in nontumorous tissues. Fifteen of the 26 patients with relative expression level of MMP-9 more than 0.34 developed tumor recurrence or metastasis, whereas only 7 of 30 patients with relative expression le velless than 0.34 developed tumor recurrence (P<0.05). There was no significant difference in the relative expression level of VEGF between patients with postoperative recurrence or metastasis and those without recurrence. AFP mRNA was detectable in 53.3 % of patients with HCC. The sensitivity and specificity of AFP mRNA as a marker to detect hematogenous dissemination of HCC cells was 81.8 % and 84.4%, respectively. Recombinant human endostatin and polyclonal an tibody against VEGF inhibited the growth of transplantable HCC in nude mice by 52.2 % and 45.7%, respectively. CONCLUSION MMP-9 expression in HCC correlates with the postoperative recurrence or metastasis of HCC. Patients with high level of MMP-9 expression in HCC are susceptible to metastasis. AFP mRNA could serve as an indicator of hematogenous spreading of HCC cells in circulation and a predictor of recur rence or metastasis of HCC. Antiangiogenesis may be an adjuvant therapy for HCC