Imbalance between cell proliferation and cellular DNA fragmentation in hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) is known for its rapid growth. This study was undertaken to determine the expression of proliferative markers, apoptosis (DNA fragmentation) and oncogene products known to regulate apoptosis (p53, bcl-2) in HCC.


METHODS
150 Chinese patients with HCC were studied (M:F 128:22, age 14-88 years). Immunohistochemistry was employed to detect cell proliferative markers (PCNA, Ki67), and oncogene products known to regulate apoptosis (p53, bcl-2). DNA fragmentation was determined by terminal dUTP nick end labeling (TUNEL).


RESULTS
98% and 95% of HCC had PCNA (median 2+) and Ki67 (median 2+) detected respectively. TUNEL labeling was detected in only a small number of tumor cells (no labeling in 11%, median 1/1000 cell labeled, range: 0-70/1000 cells). There was no correlation between TUNEL labeling and the clinical parameters (sex, age, cirrhosis, and survival) and the expression of cell proliferative markers. p53 was detected in 53% of the patients (median 1+, range: 0-4+) and bcl-2 was detected in a small proportion of tumor cells in only 13% of the HCCs (range: 0-1 +). The expression of p53 and Bcl-2 did not correlate with TUNEL labeling or the natural survival.


CONCLUSIONS
Cell proliferation in HCC is unmatched by apoptosis, accounting for the rapid growth of this tumor. This lack of apoptosis in HCC is unrelated to the expression of p53 or bcl-2 over-expression.
Wu
P C
PC
Department of Pathology, University of Hong Kong, Hong Kong.
Lau
V K
VK
Fang
J W
JW
Lai
V C
VC
Lai
C L
CL
Lau
J Y
JY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53