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Published on: April 12, 2019
Reduced expression of von Hippel-Lindau protein correlates with decreased apoptosis and high chondrosarcoma grade
Changbao Chen1, Hua Zhou, Xiaoguang Liu
1Department of Orthopaedic Surgery, Tianjin Hospital, 406 Jiefang South Road, Tianjin, 300211, China. Changbaochen@gmail.com
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.
Insights
Reduced von Hippel-Lindau (VHL) protein expression is linked to higher chondrosarcoma grade and decreased apoptosis. Further research is needed to understand its role in chondrosarcoma development.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The von Hippel-Lindau (VHL) tumor suppressor gene is frequently mutated in various cancers, but its role in chondrosarcoma is unclear.
- Understanding VHL protein (pVHL) expression is crucial for characterizing chondrosarcoma pathogenesis.
Purpose of the Study:
- To investigate pVHL expression profiles in chondrosarcoma.
- To assess the association of pVHL with clinicopathologic parameters, Bax expression, apoptosis index, and patient survival.
Main Methods:
- Real-time PCR and Western blot to quantify VHL mRNA and protein levels.
- Immunohistochemistry to evaluate pVHL and Bax protein expression in tumor samples.
- TUNEL assay for apoptosis index and Kaplan-Meier analysis for survival.
Main Results:
- VHL mRNA and protein levels were significantly reduced in chondrosarcomas compared to normal tissues.
- Decreased pVHL expression was observed in a higher proportion of chondrosarcomas than benign cartilage tumors.
- Reduced pVHL correlated positively with Bax expression and apoptosis index, and with increased tumor grade.
Conclusions:
- Reduced pVHL expression is associated with decreased apoptosis and higher chondrosarcoma grade.
- The precise relationship between these findings and chondrosarcoma pathogenesis warrants further investigation.
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