Expression of cyclin D1, cyclin E, cdk4 and loss of heterozygosity of 8p, 13q, 17p in hepatocellular carcinoma: comparison study of childhood and adult hepatocellular carcinoma.
OBJECTIVE
In hepatitis B virus-related hepatocellular carcinoma (HCC), at least 20-40 years of continuous necro-inflammation is necessary for the hepato-carcinogenesis to occur. However, HCC in childhood shows an unusually short latent period and rapid progression. In our previous report, mutation of c-met was found only in childhood HCC, but not in adult HCC. In order to determine the specific biological tumorous features of childhood HCC, a comparison study of childhood and adult HCC was performed.


METHODS
Eighteen cases of HBV positive HCC (nine children and nine adults aged more than 40 years) were selected. The expression of G1 phase regulatory proteins (cyclin D1, cyclin E and cdk4) was studied using immunohistochemical methods. Loss of heterozygosity (LOH) on chromosomal arms 8p, 13q and 17p was analyzed.


RESULTS
Cyclin D1 expression was significantly lower in childhood HCC than in adult HCC (cases of cyclin D1 expression under 3+: childhood 5/9 vs. adult 1/9, p=0.046). No difference in cyclin E and cdk4 expression was found between childhood and adult HCC. LOH frequency on 13q was relatively higher in childhood than in adult HCC (66.7% vs. 22.2%, p=0.058). LOH frequency on 8p and 17p was 44.4% and 33.3% in childhood HCC and 44.4% and 75% in adult HCC with no statistical significance between the two groups.


CONCLUSIONS
Our data suggest that childhood HCC may be less dependent on cyclin D1 protein for tumor growth and progression than adult HCC, and that the LOH on 13q may be an important feature of childhood HCC.
Kim
H
H
Department of Pathology, Seoul National University College of Medicine, Korea.
Lee
M J
MJ
Kim
M R
MR
Chung
I P
IP
Kim
Y M
YM
Lee
J Y
JY
Jang
J J
JJ
D000293:Adolescent; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002648:Child; D002877:Chromosomes, Human / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D019084:Fluorescent Antibody Technique, Indirect; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019656:Loss of Heterozygosity; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins
D018797:Cell Cycle Proteins; D019927:Cyclin E; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases