P21/WAF1 is an independent survival prognostic factor for patients with hepatocellular carcinoma after resection.
OBJECTIVE
The cyclin kinase inhibitor p21/WAF1 is regulated by p53-dependent or independent pathways and inhibits the action of proliferating cell nuclear antigen (PCNA). The prognostic role of p21/WAF1 in hepatocellular carcinoma (HCC) is ambiguous. To further clarify this, we examined the expression of three genes in HCC.


METHODS
A total of 122 resected HCC specimens were collected from 1987 to 1998. Expression of p21/WAF1, p53, and PCNA in HCC was analysed by immunohistochemistry.


RESULTS
Immunoreactivity was detectable for p21/WAF1 in 37%, and for p53 in 41.8% of HCCs. Positive expression of both genes does not relate to each other, but both are associated with a high PCNA labelling index (LI) (P<0.05) in tumour. p53 (+) is also associated with high serum alpha-foetoprotein (alphaFP) (P<0.001), tumour dedifferentiation (P=0.001) and advanced pathologic stages (P=0.017). However, p21/WAF1 (+) did not show clinicopathologic significance. Survival analysis indicated that poor prognostic factors were p21/WAF1 (-) (P=0.024), p53 (+) (P=0.008), high PCNA (P<0.001), tumour without capsule (P=0.001), poor tumour differentiation (P=0.004), advanced pathologic stage (P<0.001), and high serum alphaFP(P<0.001). Independent factors were p21/WAF1 expression, pathologic stage, and PCNA.


CONCLUSIONS
In HCC, increased proliferation index PCNA is significantly associated with positive p53 and p21/WAF1. But p21/WAF1 expression did not relate to p53 expression. P21/WAF1 (+) is a good event and serves as an independent survival prognostic factor for HCC, which is a novel finding apart from previous reports.
Kao
Jung-Ta
JT
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Chuah
Seng-Kee
SK
Huang
Chao-Cheng
CC
Chen
Chao-Long
CL
Wang
Chih-Chi
CC
Hung
Chao-Hung
CH
Chen
Chien-Hung
CH
Wang
Jing-Houng
JH
Lu
Sheng-Nan
SN
Lee
Chuan-Mo
CM
Changchien
Chi-Sin
CS
Hu
Tsung-Hui
TH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D000509:alpha-Fetoproteins / Q000378:metabolism
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins