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Reduced Expression of von Hippel-Lindau Protein Correlates with Decreased Apoptosis and High Chondrosarcoma Grade
Changbao Chen, MD, PhD1; Hua Zhou, MD, PhD2; Xiaoguang Liu, MD2; Zhongjun Liu, MD2; Qingjun Ma, MD, PhD2
1 Department of Orthopaedic Surgery, Tianjin Hospital, 406 Jiefang South Road, Tianjin, 300211, China. E-mail address: Changbaochen@gmail.com.
2 Department of Orthopaedic Surgery, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China. E-mail address for H. Zhou: zhouhua@bjmu.edu.cn. E-mail address for X. Liu: xglius@vip.sina.com. E-mail address for Z. Liu: liuzj@medmail.com.cn. E-mail address for Q. Ma: Richivaldchen@gmail.com
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Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

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Investigation performed at the Department of Orthopaedic Surgery, Peking University Third Hospital, Beijing, China

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Oct 05;93(19):1833-1840. doi: 10.2106/JBJS.I.01553
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Mutations and loss of the von Hippel-Lindau (VHL) tumor suppressor gene are associated with most renal cancers as well as several other types of human tumors, but the potential role of the VHL protein (pVHL) in patients with chondrosarcoma has not been characterized. The purpose of the present study was to investigate the expression profiles of pVHL in chondrosarcoma and its association with clinicopathologic parameters, Bax expression, the apoptosis index, and overall survival of patients with chondrosarcoma.


The messenger RNA (mRNA) and protein levels of VHL in fresh specimens from eight chondrosarcomas were studied with use of real-time polymerase chain reaction and Western blot, respectively. The protein expression of VHL and Bax was investigated by means of immunohistochemical analysis of paraffin-embedded clinical specimens from seventeen benign cartilage tumors and thirty-four chondrosarcomas. The apoptosis index in chondrosarcoma was examined by means of the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay. Curves for overall survival were drawn according to the Kaplan-Meier method, and differences were analyzed with the log-rank test. The association of pVHL expression with the clinicopathologic parameters, Bax expression, apoptosis index, and overall survival for patients with chondrosarcoma was also analyzed.


Levels of VHL protein (p = 0.005) and mRNA (p = 0.008) were significantly reduced in chondrosarcoma tissues as compared with the paired adjacent normal tissues. Immunohistochemical analysis showed decreased pVHL in a significantly higher proportion of chondrosarcomas (64.7%) than benign cartilage tumors (29.4%). pVHL expression was positively correlated with Bax expression and the apoptosis index in chondrosarcoma. Longitudinal studies of a cohort of patients with chondrosarcomas showed that decreased pVHL expression significantly correlated with increased tumor grade (p = 0.026) but was not independently predictive of overall survival.


Reduced pVHL expression was associated with decreased apoptosis and increasing chondrosarcoma grade, but the relationship between these findings and chondrosarcoma pathogenesis requires further study.

Clinical Relevance: 

Restored VHL expression could be a potential targeted therapy to treat chondrosarcoma.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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