Kampmann Eric, Altendorf-Hofmann Annelore, Gibis Sebastian, Lindner Lars H, Issels Rolf, Kirchner Thomas, Knösel Thomas
Department of Internal Medicine III, Ludwig-Maximilians-University (LMU), Munich, Germany.
Department of General, Visceral und Vascular Surgery, Friedrich-Schiller University, Jena, Germany.
Pathol Res Pract. 2015 Oct;211(10):726-30. doi: 10.1016/j.prp.2015.04.015. Epub 2015 May 21.
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.
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).
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).
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.
酪氨酸激酶是个性化医疗中很有前景的靶点，目前有新药正处于2期和3期临床试验阶段。然而，将酪氨酸激酶的表达分析作为预测性生物标志物仍不是一种标准方法。此外，仅有有限的研究在蛋白质水平上研究酪氨酸激酶受体的表达。在本研究中，我们分析了一组特征明确的软组织肉瘤中不同酪氨酸激酶受体的情况，并将结果与临床病理参数（包括生存率）相关联。
对路德维希 - 马克西米利安大学（LMU）肉瘤中心的275例软组织肉瘤进行重新研究，并根据当前的世界卫生组织分类系统进行分类。肿瘤群体包括未分化多形性肉瘤（n = 81）、平滑肌肉瘤（n = 50）、滑膜肉瘤（n = 27）、脂肪肉瘤（n = 51）、血管肉瘤（n = 43）和其他软组织肉瘤（n = 23）。
在蛋白质水平上，免疫组化检测到VEGFR1高表达的占61%，VEGFR2（KDR）高表达的占11%，VEGFR3高表达的占64%，PDGFRA高表达的占42%，PDGFRB高表达的占73%。VEGFR1 - 3和PDGFRB的高表达与更高的分级（G2 vs G3，p < 0.05）显著相关，VEGFR2高表达与患者生存率降低显著相关（p < 0.001）。
酪氨酸激酶受体在软组织肉瘤中呈现出独特的表达模式。VEGFR2（KDR）高表达与患者生存率降低显著相关。VEGFR 1 - 3和PDGFRB高表达与更高的肿瘤分级显著相关。在进行靶向治疗前可评估蛋白质特征，为合适的个性化治疗提供依据。
