title: Reduced expression of von Hippel-Lindau protein correlates with decreased apoptosis and high chondrosarcoma grade.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Reduced pVHL expression was associated with decreased apoptosis and increasing chondrosarcoma grade, but the relationship between these findings and chondrosarcoma pathogenesis requires further study.
authors: Department of Orthopaedic Surgery, Tianjin Hospital, 406 Jiefang South Road, Tianjin, 300211, China. Changbaochen@gmail.com
authors: Changbao
authors: C
authors: Chen
authors: Hua
authors: H
authors: Zhou
authors: Xiaoguang
authors: X
authors: Liu
authors: Zhongjun
authors: Z
authors: Liu
authors: Qingjun
authors: Q
authors: Ma
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D002813:Chondrosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human