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High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis.

Authors
 Bong-Kyeong Oh  ;  Haeryoung Kim  ;  Young Nyun Park  ;  Jeong Eun Yoo  ;  Jinsub Choi  ;  Kyung-Sik Kim  ;  Jae Jung Lee  ;  Chanil Park 
Citation
 LABORATORY INVESTIGATION, Vol.88(2) : 144-152, 2008 
Journal Title
 LABORATORY INVESTIGATION 
ISSN
 0023-6837 
Issue Date
2008
MeSH
Adult ; Aged ; Carcinoma, Hepatocellular/enzymology* ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Differentiation/physiology ; Female ; Humans ; Keratin-19/metabolism ; Liver Neoplasms/enzymology* ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Male ; Middle Aged ; Mitosis/physiology* ; Prognosis ; RNA, Messenger/metabolism ; Telomerase/metabolism* ; Telomere/metabolism*
Keywords
hepatocellular carcinoma ; telomere ; telomerase ; hTERT ; multipolar mitosis ; prognosis
Abstract
Telomerase reactivation and telomere maintenance are crucial in carcinogenesis and tumor progression. In this study, the relationships between telomere parameters, chromosomal instability and clinicopathological features were evaluated in hepatocellular carcinomas (HCCs). Telomere length (TL), telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA levels were measured in 49 hepatitis B virus (HBV)-related HCCs and corresponding non-tumorous tissues. The results were compared with clinicopathological data, including differentiation, multipolar mitosis (MM), anaphase bridge, immunohistochemical stain results for cytokeratin 19 (CK19) and patient outcome. TL of HCCs ranged from 4.7 to 13.1 kb, and 44.4% of HCCs showed telomere lengthening. hTERT mRNA levels and TA were closely related (P=0.008), and were significantly higher in HCCs than non-tumorous tissues. TL was significantly higher in HCCs with strong TA (P=0.048), high hTERT mRNA levels (P=0.001) and poor differentiation (P=0.041). Frequent MM was associated with poor differentiation (P=0.007) and advanced stage (P<0.001). TA was positively correlated with MM, anaphase bridges and advanced stage (P=0.019, P=0.017 and P=0.029). Thirteen (28.3%) HCCs were CK19+ and demonstrated longer telomeres than CK19- HCCs (P=0.046). Overall survival was poor in HCCs with MM >0.4 per field (P=0.016), high TA (P=0.009) and high TL ratio (HCC/non-HCC) >0.8 (P=0.044). Our results show that long telomeres, high TA and high mitotic instability are poor prognostic markers for HBV-related HCCs and their close association suggests that telomere maintenance may be important for the progression of HCCs with high chromosomal instability to more aggressive ones.
Files in This Item:
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DOI
10.1038/labinvest.3700710
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Park, Chan Il(박찬일)
Oh, Bong Kyeong(오봉경)
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Choi, Jin Sub(최진섭)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106761
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