Page 68 - ebook HCC

66 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 67
FEBRUARY 13 - 16, 2014

PREMALIGNANT LESIONS IN
HBV-CARCINOGENESIS

Young Nyun Park 1
1 Pathology, BK21 PLUS Project for Medical Science Yonsei University College of
Medicine, Seoul, Korea, South
Corresponding author’s e-mail: young0608@yuhs.ac

Introduction: Accumulating evidence strongly favors the existence of a multistep process And it was higher in HBV- than HCV-related hepatocarcinogenesis. Neoplastic cells
in hepatocarcinogenesis. In the liver, dysplastic cells may form clusters (dysplastic foci, expressing liver stem/progenitor cell markers appeared to be more involved in late rather
< 0.1 cm in diameter), which are detectable only upon microscopic examination, or nodules than earlier stage of hepatocarcinogenesis. Concerning dysplastic foci, there was a
(dysplastic nodules, DNs, usually 1cm in diameter), which are detectable macroscopically.
progressive decrease in telomere length and progressive increase in proliferative activity
BASIC SPEAKERS ABSTRACTS (SLCC) and large liver cell change (LLCC). DNs can be classified into low-grade DNs or markers including p21, p27, and p16, decreased in SLCC and were absent in HCC, BASIC SPEAKERS ABSTRACTS
Dysplastic foci consist of two types of hepatocellular changes: small liver cell change
from normal looking cirrhotic hepatocytes to LLCC, SLCC, and HCC. Cell cycle checkpoint
whereas γH2AX-DNA damage foci were present in SLCC and HCC. These data suggest
high-grade DNs on the basis of cytological and architectural atypia.
the precancerous nature of SLCC, whereas LLCC is rather heterogeneous in nature,
depending on the biological setting. HBV-related LLCC showed significantly high Tp53
Aims: The aim of this study was to characterize the premalignant nature of DNs and
labeling index, γ-H2AX labeling index, and micronuclei index; shorter telomere length;
dysplastic foci in HBV-carcinogenesis.
Methodology: The molecular and pathological features of DNs and dysplastic foci were
LLCC. The characteristics of HBV-related LLCC were more consistent with dysplastic
investigated in HBV-carcinogenesis. decreased SA-β-Gal activity; and increased net cellular gain compared to cholestatic
rather than merely reactive hepatocytes, whereas those of cholestatic LLCC were more
likely to represent a reactive change with more stringent cell cycle checkpoint control.
Results: In HBV-multistep hepatocarcinogenesis, gradual increases in the molecular
pathological characteristics of angiogenesis, telomere shortening, telomere dysfunction, Conclusions: Precancerous lesions of HCC include DNs and dysplastic foci. DNs,
TERT activation, inactivation of cell cycle checkpoints, DNA damage, chromosomal especially high grade DNs are considered as precancerous lesions of HCC. In regards to
instability, etc., were seen as the disease progressed from cirrhosis to low grade DN, high dysplastic foci, SLCC exhibits pathological characteristics of precancerous lesion, whereas
grade DN, and finally, hepatocellular carcinoma (HCC). The molecular pathological features the nature of LLCC is rather heterogeneous depending on the biological setting. HBV-
of high grade DNs were similar to those of HCC. The frequency of methylated genes, related LLCC is considered as premalignant lesion rather than merely reactive change.
including APC, RASSF1A, and SOCS1, increased in a stepwise fashion, progressing
from cirrhosis to low grade DN and high grade DN, and peaked in early HCCs. However,
progressed HCCs exhibited relatively less gene methylation than early HCCs, suggesting
that epigenetic changes occur predominantly in early stages of hepatocarcinogenesis. The
expression of liver stem/progenitor cell markers showed low levels in DNs and gradually
increased during multistep hepatocarcinogenesis, with the highest levels recorded in
progressed HCCs.