Expression and Hypomethylation of α-Fetoprotein Gene in Unicentric and Multicentric Human Hepatocellular Carcinomas

✍ Scribed by Shian-Yang Peng; Hey-Chi Hsu; Po-Lin Lai; Po-Tah Tsung; Juan-Shiu Chu; Po-Huang Lee; Ding-Shin Chen

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 825 KB
• Volume: 17
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840170108

✦ Synopsis

HEY-CHI Hsu2

The messenger RNA and DNA methylation of the a-fetoprotein gene were studied in 101 resected primary hepatocellular carcinomas, of which 93 were unicentric and 8 were multicentric. Fifty-five were 5 cm or less in diameter (small) and 46 were more than 5 cm in diameter (large). In 48.5% of the cases, we detected a-fetoprotein messenger RNA in hepatocellular carcinomas, more frequently in large (60.9%) than in small (38.2%; p < 0.00001) but not in any of the nontumorous livers. The a-fetoprotein messenger RNA was detected in 83%, 70% and 6.8% of patients with serum a-fetoprotein levels of 320 ng/ml or more, 100 to 319 ng/ml and less than 100 ng/ml, respectively. This finding suggests that a-fetoprotein gene expression in hepatocellular carcinoma contributes to the serum a-fetoprotein elevation in patients with hepatocellular carcinoma. a-Fetoprotein messenger RNA appeared as a major band of 2.4 kb, with two minor species of about 6.5 and 3.6 kb in the hepatocellular carcinoma and the fetal liver. Hypomethylation of the 5' end of the a-fetoprotein gene was detected in 78.3% of hepatocellular carcinomas expressing a-fetoprotein messenger RNA but infrequently (16.7%) in hepatocellular carcinomas with no detectable a-fetoprotein messenger RNA (p < 0.0003). This finding suggests that hypomethylation at the 5' region of the gene is associated with a-fetoprotein gene reexpression in hepatocellular carcinoma. The a-fetoprotein gene expression helped to differentiate unicentric from multicentric hepatocellular carcinomas and to identify other hidden a-fetoprotein-secreting hepatocellular carcinomas. The a-fetoprotein gene expression occurred more often in patients younger than 30 yr old (100% vs. 41.2%; p < 0.002), in HBsAg-seropositive patients (53.2% vs. 33.3%; p < 0.03) and in patients with poorly differentiated hepatocellular carcinoma (56% vs. 23.1%;