Ko-Expression von VEGF und bFGF ist assoziiert mit einer erhöhten Gefäßdichte in Kopf-Hals-Karzinomen[1]

Zusammenfassung

Hintergrund: Sowohl der Vascular Endothelial Growth factor (VEGF) als auch der basic Fibroblast Growth Factor (bFGF) gelten als wichtige Regulatoren der Gefäßneubildung (Angiogenese) im Tumorgewebe. Die Expression beider Faktoren konnte bereits in verschiedenen Karzinomen gezeigt werden. Ziel unserer Untersuchungen war die Rolle einer Ko-Expression dieser beiden Faktoren auf die Tumor-Angiogenese. Material und Methoden: Untersucht wurden 51 primäre Plattenepithelkarzinome aus dem Kopf-Hals-Bereich auf Expression von VEGF und bFGF sowie von Willebrand Faktor (vWF) als Endothelmarker mittels Standard-Immuno-Peroxidase-Technik. Die Quantifizierung der Gefäßzahl erfolgte unter dem Lichtmikroskop (200 ×) innerhalb einer „hot spot area” des Tumors. Ergebnisse: Bei 25 Karzinomen fanden wir eine Ko-Expression beider Faktoren (VEGF +/bFGF +), während 6 Karzinome nur VEGF und 13 Karzinome nur bFGF exprimierten. Sieben Tumore zeigten keine Expression der Faktoren (VEGF -/bFGF -). Karzinome, welche beide Faktoren ko-exprimierten, zeigten eine signifikant erhöhte mittlere Gefäßdichte (88,3 ± 24,4) gegenüber Karzinomen, die nur VEGF (77 ± 16,8) bzw. nur bFGF (71,1 ±15,8) exprimierten oder beide Faktoren nicht (51,1 ± 13,4) exprimierten. Schlussfolgerung: Die Korrelation der Ko-Expression von VEGF und bFGF mit einer erhöhten Gefäßdichte in Kopf-Hals-Karzinomen hebt die wichtige Rolle dieser Faktoren für die Tumor-Angiogenese hervor. Die Ergebnisse unterstreichen die Hypothese einer synergistischen Wirkung der beiden Faktoren beim Prozess der Neovaskularisierung.

Co-Expression of VEGF and bFGF is Associated with Increased Microvessel Density in Head and Neck Squamous Cell Carcinoma

Background: Angiogenesis is crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to correlate with metastasis and aggressiveness. Vascular endothelial growth factor (VEGF) and basic Fibroblast Growth Factor (bFGF) are known to have potent angiogenic activity. Their expression has been identified in a wide variety of malignancies including head and neck squamous cell carcinoma (HNSCC). Aim of our study was to investigate the role of co-expression of VEGF and bFGF for angiogenesis in HNSCC. Material and Methods: Cryostat sections of 51 primary HNSCC were immunostained for VEGF and bFGF using a standard streptavidin-biotin complex procedure. To evaluate angiogenesis, endothelial cells were stained immunohistochemically using anti-vWF polyclonal antibody. Microvessels were quantified by counting vessels in a × 200 field in the most vascular area of the tumor. Results: 25/51 (49%) of the investigated carcinomas showed co-expression of both factors (VEGF +/bFGF +), while 6/51 (11.7 %) carcinomas only expressed VEGF and 13/51 (25.5 %) carcinomas expressed bFGF. 7/51 (13.7 %) tumors showed no expression of these factors (VEGF -/bFGF -). Carcinomas with a co-expression of VEGF and bFGF showed a significantly increased mean microvessel density (88.3 ± 24.4) compared to tumors expressing only VEGF (77 ±16.8) or bFGF (71.1 ± 15.8) (p = 0.022) or tumors with no expression of both factors (51.1 ± 13.4) (p < 0.001). The association of VEGF and bFGF expression level was not significant (p = 0.178). Conclusions: The positive correlation of the co-expression of angiogenic VEGF and bFGF with increased microvessel density underlines the importance of both factors for tumor angiogenesis in HNSCC. VEGF and bFGF might act cooperatively in the process of neovascularization in human head and neck cancer.

bFGF - VEGF - Angiogenese - Kopf-Hals-Karzinom

Vascular endothelial growth factor - Basic fibroblast growth factor - Angiogenesis - Head and neck cancer

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01 Diese Arbeit wurde vorgestellt im Rahmen der 83. Jahrestagung der Vereinigung Südwestdeutscher Hals-Nasen-Ohrenärzte, Heidelberg, 23. - 25. September 1999.