In addition, we correlated the capacity of alpha-fetoprotein isolates from various hepatoma and fetal sources to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate.
Younger patients with HCC (less than 60 yr old) were more significantly associated with elevated serum AFP (P less than 0.0001) and serum HBsAg (P less than 0.0001) than were older (greater than or equal to 60 yr old) patients.
A case of a young white female with AT who developed hepatocellular carcinoma along with significantly elevated levels of alpha fetoprotein is presented.
This DNA showed a restriction map that was indistinguishable from that of the clone obtained from the hepatoma described above, demonstrating that no gross rearrangements of the intergenic DNA sequence are involved in control of expression of the AFP and albumin genes.
Implantation of the cells into athymic mice was followed by the growth of hepatocellular carcinomas and the appearance of human alpha-fetoprotein in the mouse serum.
The serum alpha-fetoprotein was elevated in all 20 primary hepatocellular carcinoma patients, and the average survival of these cases after diagnosis was 4.7 months.
Similarities include failure to thrive with hypoproteinemia, micronodular cirrhosis, alpha-fetoprotein positive hepatocellular carcinoma, renal Fanconi syndrome with renal tubular ectasia, hypermethioninemia, and hypoglycemia associated with islet cell hyperplasia.
DNase I footprinting and competition gel retardation assays showed that a sequence with an AT-rich core (AT motif) in the pre-S1 promoter region interacts with AFP1, a hepatoma nuclear factor that binds to the alpha-fetoprotein enhancer and promoter.
Annual determination of alpha-fetoprotein and abdominal computed tomography (CT) scan may detect the development of a hepatocellular carcinoma in such cases while they are still resectable.
The silencer functions in the presence of positive transcription factors and may play a key role in developmental repression as well as variable expression of the AFP gene in hepatomas.
Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma.
These findings suggest that c-myc amplification is not an uncommon event in human hepatocarcinogenesis, occurs more frequently in young patients who have an elevated serum AFP level or HBV infection, and is related to the biologic behavior of HCC.
The p53 protein, which was detected in 58 HCCs (31.5%), was overexpressed more frequently in HCC with elevated serum alpha-fetoprotein level (37.9 versus 25%, P < 0.04), in large HCC (39.0 versus 25.5%, P < 0.03), and in invasive HCC (35.1 versus 13.3%, P < 0.01).
The alpha-fetoprotein gene expression helped to differentiate unicentric from multicentric hepatocellular carcinomas and to identify other hidden alpha-fetoprotein-secreting hepatocellular carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
From these results, we conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.
These results suggest that the extremely proximal promoter region of the AFP gene where glucocorticoid-responsive element and HNF-1 binding sites exist is not responsible for the re-expression of AFP in HCC.
This study was conducted to detect abnormal levels of several proto-oncogenes (c-jun, c-fos, c-H-ras) and of the p53 and the alpha-fetoprotein gene in the liver during cirrhosis, a pathological process which predisposes to the development of hepatocarcinoma.