[WAF1/CIP1 gene expression in human hepatocellular carcinoma and its relationship with p53 mutation].
OBJECTIVE
To study the WAF1 gene expression in human hepatocellular carcinoma(HCC) and its relationship with p53 mutation.


METHODS
Using semiquantitative reverse transcriptase-polymerase chain reaction(RT-PCR) and immunohistochemistry, the expression of WAF1 and p53 in 32 HCC samples and their surrounding liver tissues and 5 normal liver tissues was detected respectively.


RESULTS
The expression level of WAF1 mRNA in HCC samples was lower than that in paratumor liver tissues(1.06 U +/- 0.37 U vs 1.30 U +/- 0.37 U, P < 0.01) and its positive rate of p21WAF1 was also lower than that in paratumor liver tissues(53.1% vs 100%, P < 0.01). The expression level of WAF1 mRNA in HCC samples with intra-hepatic metastatic lesions was lower than that without intra-hepatic metastatic lesions(0.92 U +/- 0.33 U vs 1.24 U +/- 0.35 U, P < 0.01) and its positive rate of p21WAF1 was also lower than that without intra-hepatic metastatic lesions(33.3% vs 78.6%, P < 0.05). The expression level of WAF1 mRNA in HCC samples with p53 mutation was lower than that without p53 mutation (0.92 U +/- 0.28 U vs 1.16 U +/- 0.40 U, P < 0.05) and its positive rate of p21WAF1 was also lower than that without p53 mutation(15.4% vs 78.9%, P < 0.01). The percentage of cells in S-phase in p21WAF1-positive HCC samples was lower than that in p21WAF1-negative HCC samples(44.57% +/- 7.56% vs 51.83% +/- 8.51%, P < 0.01). However, no significant difference in expression of WAF1 mRNA and p21WAF1 in HCC samples was found in other clinical pathological parameters such as the degree of differentiation, the histological pattern, the size of tumors, the status of capsule in tumors and the formation of tumor thrombus of portal vein. The expression level of WAF1 mRNA in normal liver tissues was strikingly lower(0.17 U +/- 0.06 U), and the immunohistochemical staining of p21WAF1 in all normal liver tissues was positive(100%).


CONCLUSIONS
The expression of WAF1 gene in HCC is predominantly regulated by dependence on p53 and the reduced WAF1 expression may participate in the carcingenesis and progression of HCC and the mechanisms of infiltration and metastasis of HCC.
Zhu
B
B
Hepatobiliary Surgical Institute, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai.
Cong
W
W
Wang
H
H
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger