Angiogenesis in Ocular and Extraocular Sebaceous Carcinoma
Ferdinand Toberer, Holger A. Haenssle, Arno Rütten, Dmitry Kazakov, Liubov Kastnerova, Alexander Enk, Wolfgang Hartschuh, Ines Bertlich, Julia Hartmann, Martin Laimer, Wolfgang Weyers, Peter Helmbold, Heinz Kutzner
To shed more light on the pathogenesis of sebaceous carcinoma, we analysed the expression of proteins related to angiogenesis in 18 ocular and 22 extraocular sebaceous carcinomas using a broad panel of immunohistochemical markers. To quantify the expression of D2-40, vascular endothelial growth factor, vascular endothelial growth factor receptor-2 and -3, we calculated a quantification score by considering the percentage of positive tumour cells (0=0%, 1=up to 1%, 2=2–10%, 3=11–50%, and 4=>50%) in relation to the staining intensity (0=negative, 1=low, 2=medium, and 3=strong). Additionally, lymphatic microvessel density in the D2-40 stained sections was counted. Vascular endothelial growth factor receptor-3 (quantification score 9.42 ± 2.94) was significantly more strongly expressed than vascular endothelial growth factor receptor-2 (quantification score 2.15 ± 2.42, p < 0.001). Furthermore, epidermal vascular endothelial growth factor expression was negatively correlated with the intratumoural lymphatic vessel density, and the ratio of small lymphatics to large lymphatics was much higher in intratumoural tissue than in paratumoural tissue and in intraindividual control tissue, suggesting a lymphangiogenetic potential of sebaceous carcinoma.
Sebaceous carcinoma represents a rare cutaneous tumour that may arise ocular and extraocular. We analysed the expression of proteins related to angiogenesis in 18 ocular and 22 extraocular sebaceous carcinomas using a broad panel of immunohistochemical markers including D2-40, vascular endothelial growth factor (VEGF), VEGFR-2 and VEGFR-3. We found an increased intratumoural ratio of small lymphatics to large lymphatics and a negative correlation between epidermal VEGF expression and the intratumoural density of lymphatics underlining the hypothesis that sebaceous carcinoma may induce new lymphatic vessels. Additionally, VEGFR-3 expression was significantly higher than VEGFR-2 expression in both ocular and extraocular tumours.