Expression of p53, Bcl-2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma.
BACKGROUND
Hepatocellular carcinoma is one of the most common malignant tumors that carry a poor prognosis. To improve the long-term outlook for HCC, an accurate prognosis is important.


OBJECTIVE
To study the immunohistochemical expressions of p53, Ki67, Bcl-2, VEGF and PCNA and their potential role as prognostic factors in patients with radical resection of hepatocellular carcinoma.


METHODS
Forty-seven formalin-fixed paraffin-embedded tumor samples from patients with HCC receiving liver resection were investigated immunohistochemically for the expression of cellular proliferation markers PCNA, Ki67, p53, Bcl-2 and VEGF and their correlation with tumor characteristics and survival time after resection.


RESULTS
p53 was expressed in a higher percentage (85.7 vs. 42.1%) in undifferentiated histological tumor grades (Edmondson Steiner G3/G4 vs. G1/G2). Patients with p53 accumulating tumors showed a worse survival than patients with p53 non-accumulating tumors (median 9.5 vs. 16.5 months). Over-expression of VEGF was found in 38.3% of all HCCs. VEGF expression was significantly correlated with p53 expression and recurrence rates. The results showed that the labeling index of PCNA and expression of p53 are correlated. The high labeling index of PCNA or over-expression of p53 resulted in high risk of tumor recurrence, more aggressive growth and poor survival.


CONCLUSIONS
High labeling index of PCNA, p53 nuclear accumulation and VEGF high expression are associated with poor survival in patients with HCC.
Stroescu
Cezar
C
Fundeni Clinical Institute - Department of General Surgery and Liver Transplantation, Bucharest, Fundeni Clinical Institute, Sos. Fundeni no 258, Bucharest, Romania. cezar.stroescu@gmail.com
Dragnea
Adrian
A
Ivanov
Bogdan
B
Pechianu
Catalin
C
Herlea
Vlad
V
Sgarbura
Olivia
O
Popescu
Andra
A
Popescu
Irinel
I
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A