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VEGFR2 predicts decreased patients survival in soft tissue sarcomas
Eric Kampmann1, Annelore Altendorf-Hofmann2, Sebastian Gibis1
1Department of Internal Medicine III, Ludwig-Maximilians-University (LMU), Munich, Germany.
Aims:
Tyrosine kinases are promising targets for personalized medicine, and new drugs are currently in phase 2 and phase 3 clinical trials. However, expression analysis of tyrosine kinases as predictive biomarkers is still not a standard approach. Furthermore, only limited studies have investigated the expression of tyrosine kinase receptors on the protein level. In this study, we analysed a well-characterised group of soft tissue sarcomas for different tyrosine kinase receptors and correlated the results with clinicopathological parameters, including survival.
Methods:
275 soft tissue sarcomas of our Sarcoma center at the Ludwig-Maximilians-University (LMU) were reinvestigated and categorized according to the current WHO classification system. The tumor collective included undifferentiated pleomorphic sarcomas (n=81), leiomyosarcomas (n=50), synovial sarcomas (n=27), liposarcomas (n=51), angiosarcomas (n=43) and other soft tissue sarcomas (n=23).
Results:
On protein levels, high expression of VEGFR1 was detected immunohistochemically in 61%, VEGFR2 (KDR) in 11%, VEGFR3 in 64%, PDGFRA in 42% and PDGFRB in 73%. High expression of VEGFR1-3 and PDGFRB was significantly correlated with higher grading (G2 vs G3, p<0.05), and high VEGFR2 was significantly correlated with decreased patients' survival (p<0.001).
Conclusions:
Tyrosine kinase receptors showed a distinct expression pattern in soft tissue sarcomas. High expression of VEGFR2 (KDR) is significantly associated with decreased patients' survival. High VEGFR 1-3 and PDGFRB are significantly correlated with higher tumor grading. Protein signatures might be evaluated before targeted therapy to give a rationale for an eligible personalized therapy.
Insights
High expression of tyrosine kinase receptors like VEGFR2 is linked to poorer survival in soft tissue sarcomas. Protein analysis may guide personalized cancer therapy decisions.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Research
Background:
- Tyrosine kinases are key targets for personalized cancer medicine.
- Expression analysis of tyrosine kinases as predictive biomarkers is not yet standard practice.
- Limited studies have investigated tyrosine kinase receptor expression at the protein level.
Purpose of the Study:
- To analyze tyrosine kinase receptor expression in soft tissue sarcomas.
- To correlate receptor expression with clinicopathological parameters and patient survival.
Main Methods:
- Investigated 275 soft tissue sarcomas categorized by WHO classification.
- Utilized immunohistochemistry to assess protein expression of VEGFR1, VEGFR2 (KDR), VEGFR3, PDGFRA, and PDGFRB.
- Correlated findings with tumor grade and patient survival data.
Main Results:
- High expression of VEGFR1 (61%), VEGFR3 (64%), and PDGFRB (73%) was frequently detected.
- High expression of VEGFR1-3 and PDGFRB correlated significantly with higher tumor grading (G2 vs G3).
- Elevated VEGFR2 (KDR) expression was significantly associated with decreased patient survival (p<0.001).
Conclusions:
- Distinct expression patterns of tyrosine kinase receptors exist in soft tissue sarcomas.
- VEGFR2 (KDR) high expression indicates poorer patient survival.
- VEGFR1-3 and PDGFRB expression levels correlate with tumor grade, suggesting potential as predictive biomarkers for personalized therapy.
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