Prognostic significance of serum anti-p53 antibody in patients with hepatocellular carcinoma.
OBJECTIVE
Abnormalities of the p53 gene can lead to the production of anti-p53 antibody in the serum of cancer patients. We evaluated the prognostic significance of anti-p53 antibody in 86 patients with hepatocellular carcinoma (HCC) in comparison with clinicopathological factors: age, sex, etiology, smoking and drinking habits, history of blood transfusion, presence of encephalopathy and ascites, Child classification, Pugh score, bilirubin, albumin, prothrombin time, indocyanine green retention time at 15 min (ICG), underlying liver disease, alpha-fetoprotein (AFP), tumor size, number of tumors, differentiation degree of HCC, presence of extrahepatic metastasis and therapy for HCC.


METHODS
The serum anti-p53 antibody in 86 patients with HCC, 20 with chronic hepatitis (CH) and 20 with liver cirrhosis (LC) was measured by an enzyme-linked immunosorbent assay (ELISA). A single-strand conformation polymorphism-polymerase chain reaction (SSCP-PCR) analysis and loss of heterozygosity (LOH) study of the p53 gene were performed using 8 tissue samples of 8 HCC from four antibody-positive and four antibody-negative patients. The survival probabilities were assessed by the Kaplan-Meier technique, and a Cox regression analysis was used to identify the independent factors for prognosis.


RESULTS
Anti-p53 antibody was positive in 32% (28 of 86) of the sera from patients with HCC, but in none of the 20 with CH and 20 with LC. p53 antibody positivity was associated with bilirubin and the number of tumors (p=0.027 and p=0.018, respectively). Overall survival was shorter in the HCC patients with p53 antibody than in those without p53 antibody (p<0.02). Bilirubin, p53 antibody, AFP and ICG were found to be significant prognostic factors by univariate analysis. A Cox multivariate analysis showed that bilirubin and p53 antibody were independent prognostic variables (p<0.0001 and p=0.003, respectively). In four antibody-positive patients, mutation and LOH of the p53 gene were detected in one patient and two patients, respectively. In contrast, only one of four antibody-negative patients exhibited LOH of the p53 gene.


CONCLUSIONS
Serum anti-p53 antibody could be a useful prognostic factor in patients with HCC.
Shiota
G
G
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Kishimoto
Y
Y
Suyama
A
A
Okubo
M
M
Katayama
S
S
Harada
K
K
Ishida
M
M
Hori
K
K
Suou
T
T
Kawasaki
H
H
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000276:immunology*; D011379:Prognosis; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53