Format

Send to

Choose Destination
Dig Dis Sci. 2015 Feb;60(2):420-6. doi: 10.1007/s10620-014-3364-3. Epub 2014 Nov 8.

Evidence for heightened hexokinase II immunoexpression in hepatocyte dysplasia and hepatocellular carcinoma.

Author information

1
Pathology, College of Medicine, Cancer Center, University of Illinois Hospital and Health Science System, 840 South Wood Street Room 130M/C 847, Chicago, IL, 60612, USA, grace.guzman.md@gmail.com.

Abstract

BACKGROUND:

Normal hepatocytes exhibit low-affinity hexokinase (glucokinase [HKIV]), but during oncogenesis, there is a switch from HKIV to HKII expression. The aims of this study were to compare the immunoexpression of HKII in non-dysplastic cirrhosis (NDC), liver cell change/dysplasia in cirrhosis (LCD), HCC, and normal liver control tissues, and to correlate HKII expression with clinical and histopathological parameters.

DESIGN:

Immunohistochemistry was performed on a liver cancer progression tissue array consisting of specimens from explants with cirrhosis, including 45 tissue samples with HCC, 108 without HCC, 143 with LCD, and 8 normal liver control tissues. HKII expression was quantified as positive pixel counts/square millimeter (ppc/mm(2)) by image analysis.

RESULTS:

There was a stepwise increase in HKII level from normal liver tissue to NDC, to LCD, and to HCC (p = 0.001). HKII levels were significantly higher in areas of LCD versus NDC (p ≤ 0.001), and in LCD and HCC versus NDC (p = 0.007). HKII levels were similar in LCD and HCC (p = 0.124). HKII levels were higher in grade 2-4 versus grade 1 HCCs (p = 0.044), and in pleomorphic versus non-pleomorphic HCC variants (p = 0.041). Higher levels of HKII expression in LCD and HCC versus NDC and in higher tumor grade remained significant in multivariate analysis.

CONCLUSIONS:

Higher levels of HKII immunoexpression in LDC and HCC compared with NDC suggest that upregulation of HKII occurs during the process of hepatocarcinogenesis in humans. In HCC, higher levels of HKII are associated with more aggressive histological features.

PMID:
25381201
PMCID:
PMC4323170
DOI:
10.1007/s10620-014-3364-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center