Receptor activator of nuclear factor-κB ligand (RANKL) expression in hepatocellular carcinoma with bone metastasis

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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. Published by Springer Science+Business Media, Inc.

Original languageEnglish
Pages (from-to)1191-1199
Number of pages9
JournalAnnals of Surgical Oncology
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 1 2007

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Cytoplasmic and Nuclear Receptors
Hepatocellular Carcinoma
Neoplasm Metastasis
Ligands
Bone and Bones
Bone Development
RANK Ligand
Reverse Transcriptase Polymerase Chain Reaction
Neoplasms
Messenger RNA
Hepatitis C Antibodies
Bone Remodeling
Liver
Bone Resorption
Hepatitis B Surface Antigens
Liver Cirrhosis
Paraffin
Formaldehyde
Disease-Free Survival
Survival Rate

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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Receptor activator of nuclear factor-κB ligand (RANKL) expression in hepatocellular carcinoma with bone metastasis. / Sasaki, Atsushi; Ishikawa, Kenji; Haraguchi, Naotsugu; Inoue, Hiroshi; Ishio, Tetsuya; Shibata, Kohei; Ohta, Masayuki; Kitano, Seigo; Mori, Masaki.

In: Annals of Surgical Oncology, Vol. 14, No. 3, 01.03.2007, p. 1191-1199.

Research output: Contribution to journalArticle

Sasaki, A, Ishikawa, K, Haraguchi, N, Inoue, H, Ishio, T, Shibata, K, Ohta, M, Kitano, S & Mori, M 2007, 'Receptor activator of nuclear factor-κB ligand (RANKL) expression in hepatocellular carcinoma with bone metastasis', Annals of Surgical Oncology, vol. 14, no. 3, pp. 1191-1199. https://doi.org/10.1245/s10434-006-9277-4
Sasaki, Atsushi ; Ishikawa, Kenji ; Haraguchi, Naotsugu ; Inoue, Hiroshi ; Ishio, Tetsuya ; Shibata, Kohei ; Ohta, Masayuki ; Kitano, Seigo ; Mori, Masaki. / Receptor activator of nuclear factor-κB ligand (RANKL) expression in hepatocellular carcinoma with bone metastasis. In: Annals of Surgical Oncology. 2007 ; Vol. 14, No. 3. pp. 1191-1199.
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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. Published by Springer Science+Business Media, Inc.",
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AU - Sasaki, Atsushi

AU - Ishikawa, Kenji

AU - Haraguchi, Naotsugu

AU - Inoue, Hiroshi

AU - Ishio, Tetsuya

AU - Shibata, Kohei

AU - Ohta, Masayuki

AU - Kitano, Seigo

AU - Mori, Masaki

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AB - 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. Published by Springer Science+Business Media, Inc.

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