Original Articles
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 15, 2000; 6(1): 61-65
Published online Feb 15, 2000. doi: 10.3748/wjg.v6.i1.61
Recurrence or metastasis of HCC: predictors, early detection and experimental antiangiogenic therapy
Yang-Fu Jiang, Zhi-Hua Yang, Jin-Qun Hu
Yang-Fu Jiang, Zhi-Hua Yang, Jin-Qun Hu, Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
Yang-Fu Jiang, male, born on 1971-03-28 in Chongqing, graduated from West-China University of Medical Sciences in 1993, got Ph.D. at Peking Union Medical College in 1999. Now postdoctoral fellow at Albert Einstein College of Medicine, U.S.A, having 4 papers published.
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Zhi-Hua Yang, Department of Molecular Biology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100021, China. Zhyang@public.bta.net.cn
Telephone: +86-10-67781331 Ext. 8439 Fax: +86-10-67782259
Received: July 3, 1999
Revised: September 2, 1999
Accepted: September 15, 1999
Published online: February 15, 2000

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.

Keywords: carcinoma, hepatocellular, neoplasm metasta sis, angiogenesis, liver neoplasms