Hepatocellular Carcinoma
Hepatocellular carcinoma is one of the most common cancers
worldwide. It is very common in Southeast Asia where aflatoxin B1 food contamination and
hepatitis B virus infection are common. These two factors have been linked to the
development of hepatocellular carcinoma (HCC) from epidemiologic studies. In Japan and
Italy, HCC has also been linked to chronic hepatitis C virus infection. In the United
States, there are 6,000–9,000 new cases of HCC per year.
Mutations/deletions of the tumor suppressor gene, p53 (located on
the short arm of chromosome 17), which is critical in the induction of apoptosis are
common in HCC from a number of geographic regions. A number of mutational
"hot–spots" and deletions have been identified. Since p53 is an important
factor in the induction of apoptosis, it is not surprising that mutation of this gene is
common in HCC (range from 5% to 50%). In a recent study, restoration of the wild type p53
gene into HCC cell lines induced apoptosis, further supporting that mutation/deletion p53
may play a role in HCC carcinogenesis.
What causes the p53 mutations? Epidemiologic studies have linked
aflatoxin B1 exposure and p53 mutation, with the mutational "hot–spot" in
position 249 (G?T transversion). This transversion is common in HCC in patients from
mainland China, Africa, and Mexico where aflatoxin B1 contamination of food is high, and
rare in Hong Kong, Singapore, Japan, Europe and in Caucasian patients in the United
States, where food contains little or no aflatoxin B1. This epidemiologic observation is
supported by an in vitro study which shows the ability of aflatoxin B1 to induce this
specific mutation. In other areas, different patterns of p53 mutations occur in patients
with HCC. Interestingly, the mutant p53 with codon 249 substitution (changing from
arginine to serine) is reported to enhance mitotic activity, suggesting that certain p53
mutant may directly promote carcinogenesis.
Numerous treatment options are available for patients with
hepatocellular carcinoma. Today, resection remains the mainstay of treatment for most
patients with hepatocellular carcinomas arising in noncirrhotic liver or Child-Pugh A
patients with stable cirrhosis. Vascular invasion, defined as lymphatic or hepatic and/or
portal vein permeation by malignant cells, is the most important predictor of survival
following resection. Other options range from local ablation (radiofrequency, alcohol,
etc…) in small tumors to systemic or arterial chemotherapy in advanced hepatocellular
carcinoma. The role of transplantation is controversial.
