Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?
OBJECTIVE
Mutant p53 gene has lost its tumor suppression function and is considered to be a very important step in hepatocellular carcinoma development. We propose that the mutant p53 gene plays a role in its invasiveness and prognosis after resection.


METHODS
A case-controlled study.


METHODS
A referral center.


METHODS
Seventy-nine consecutive patients who underwent surgical resection for hepatocellular carcinoma entered this study.


METHODS
Tissue sections of resected hepatocellular carcinoma (deparaffinized and rehydrated from formalin-fixed and paraffin-embedded sections) were incubated with antihuman p53 monoclonal antibody and immunostained. The p53 result was scored without prior knowledge of the patients' status. A 10% immunopositivity was regarded as the threshold value.


METHODS
The immunopositive rate of p53 was 69.6% (55 of 79 patients). The clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum alpha-fetoprotein, and Child-Pugh class); the histological variables (size, capsule, vascular permeation; grade of differentiation, and multinodularity); and postoperative course (recurrence, tumor-free interval, death, and survival period) were correlated with p53 immunopositivity.


RESULTS
From univariate analysis, more patients with p53 positivity were male (92.7 vs 0%) (P<.001); had vascular permeation (80% vs 50%) (P =.007) (odds ratio [OR], 4.0); no complete capsule (83.6% vs 62.5%) (P =.04) (OR, 3.1); and daughter nodules (90.9% vs 70.8%) (P =.04) (OR, 4.1) than patients with negative p53 staining. From multivariate analysis, only sex and vascular permeation remained significant (P =.001 and P =.008, respectively). Although more patients with p53 positivity had tumor recurrence (78% vs 50%) (P =.01) and death (64% vs 33%) (P =. 01), the Cox proportional hazards model showed that p53 overexpression had only weak correlations with tumor-free interval and survival time (P =.09 and P =.08, respectively).


CONCLUSIONS
Our results show that the biological behavior of the mutant p53 gene is strongly related to the invasiveness of hepatocellular carcinoma and may also influence the postoperative course. We suggest that the immunopositivity of the mutant p53 gene has a predictive role in the prognosis of patients with resected hepatocellular carcinoma.
Jeng
K S
KS
Department of Surgery, Mackay Memorial Hospital, No. 92, Section 2, Chung-San North Road, Taipei, Taiwan, Republic of China. issheen@gcn. net.tw
Sheen
I S
IS
Chen
B F
BF
Wu
J Y
JY
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models