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01-03-2007

Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Hepatocellular Carcinoma With Bone Metastasis

Authors: Atsushi Sasaki, MD, Kenji Ishikawa, MD, Naotsugu Haraguchi, MD, Hiroshi Inoue, MD, Tetsuya Ishio, MD, Kohei Shibata, MD, Masayuki Ohta, MD, Seigo Kitano, MD, Masaki Mori, MD

Published in: Annals of Surgical Oncology | Issue 3/2007

Abstract

Background

Although receptor activator of nuclear factor-κB ligand (RANKL) seems to be involved in the development of bone metastases in several malignant tumors, its role in hepatocellular carcinoma (HCC) has not been investigated.

Methods

We retrospectively examined the immunohistochemical expression of RANKL in formalin-fixed, paraffin-embedded resected specimens obtained from 96 patients with HCC with (n = 16) and without (n = 80) bone metastases. In addition, tumor RANKL mRNA expression was evaluated by reverse transcriptase–polymerase chain reaction (RT-PCR) in five selected patients. We analyzed the relationship between RANKL expression level, bone metastasis development, and survival rate of patients with HCC after hepatic resection.

Results

Of the 96 patients with HCC, serum hepatitis C virus antibody was detected in 43.5% of patients and hepatitis B surface antigen in 29.5% of patients. Thirty-three patients (36.5%) also had liver cirrhosis. Immunohistochemical analysis showed that RANKL protein was present in 10 (62.5%) of 16 patients with HCC with bone metastasis compared with 21 (26.3%) of 80 patients with HCC without bone metastasis; we found that RANKL expression was statistically significantly correlated to bone metastasis development (P < .01). RANKL mRNA expression was confirmed by RT-PCR in patients positive for RANKL protein expression by immunohistochemistry. The 5-year cancer-related (P < .01) and disease-free survival (P < .01) rates after hepatic resection were statistically significantly worse in patients positive for RANKL expression compared with RANKL-negative patients.

Conclusions

Some HCC cells produced the crucial bone resorption regulator RANKL. Because RANKL modulates bone turnover, its presence would have profound implications for the establishment and development of bone metastases.

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Title: Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Hepatocellular Carcinoma With Bone Metastasis
Authors: Atsushi Sasaki, MD
Kenji Ishikawa, MD
Naotsugu Haraguchi, MD
Hiroshi Inoue, MD
Tetsuya Ishio, MD
Kohei Shibata, MD
Masayuki Ohta, MD
Seigo Kitano, MD
Masaki Mori, MD
Publication date: 01-03-2007
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 3/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-006-9277-4

At a glance: The STEP trials

Springer Medicine

Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Hepatocellular Carcinoma With Bone Metastasis

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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