Acta Dermato-Venereologica 99-13CompleteContent | Page 18

1270 INVESTIGATIVE REPORT Angiogenesis in Ocular and Extraocular Sebaceous Carcinoma Ferdinand TOBERER 1 , Holger A. HAENSSLE 1 , Arno RÜTTEN 2 , Dmitry KAZAKOV 3 , Liubov KASTNEROVA 3 , Alexander ENK 1 , Wolfgang HARTSCHUH 1 , Ines BERTLICH 1 , Julia HARTMANN 1 , Martin LAIMER 4 , Wolfgang WEYERS 5 , Peter HELMBOLD 1 and Heinz KUTZNER 2 Department of Dermatology, Venereology and Allergology, University Medical Center, Ruprecht-Karls-University Heidelberg, Heidelberg, Dermatopathology, Bodensee, Friedrichshafen, Germany, 3 Sikl’s Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic, 4 Department of Dermatology, University Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria, and 5 Center for Dermatopathology Freiburg, Freiburg, Germany 1 2 To shed more light on the pathogenesis of sebaceous carcinoma, we analysed the expression of proteins re­ lated to angiogenesis in 18 ocular and 22 extraocular sebaceous carcinomas using a broad panel of immu­ nohistochemical markers. To quantify the expression of D2-40, vascular endothelial growth factor, vascular endothelial growth factor receptor-2 and -3, we cal­ culated a quantification score by considering the per­ centage 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 (quanti­ fication score 9.42  ±  2.94) was significantly more stron­ gly 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. Key words: angiogenesis; lymphatic vessels; sebaceous carci- noma. Accepted Oct 14, 2019; E-published Oct 14, 2019 Acta Derm Venereol 2019; 99: 1270–1274. Corr: Ferdinand Toberer, Department of Dermatology, Venereology and Allergology, University Medical Center, Ruprecht-Karls-University, Im Neuenheimer Feld 440, DE-69120 Heidelberg, Germany. E-mail: ferdi- [email protected] S ebaceous carcinoma (SC) represents a rare cuta- neous adnexal neoplasm that may arise as ocular or extraocular SC (1). Extraocular SC is rare (25% of reported cases) and mostly affects the head and neck (2). According to a review including 1,349 cases of SC, the median age at diagnosis was 73 years, and a slight male predominance (54% men and 46% women) was noted (3). Both ocular and extraocular SC have the capability for regional and distant metastases (4). The tendency for regional metastases is increased in ocular SC. Ne- vertheless, the cancer-specific mortality rates are similar among all anatomic locations (4). Although surgery is doi: 10.2340/00015555-3342 Acta Derm Venereol 2019; 99: 1270–1274 SIGNIFICANCE Sebaceous carcinoma represents a rare cutaneous tumour that may arise ocular and extraocular. We analysed the ex- pression 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 lympha- tics 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. the treatment of choice for local disease, radiation and systemic chemotherapy are options for recurrent and metastatic disease (4). SC may arise in the context of Muir-Torre syndrome (MTS) or in association with prior irradiation, immuno­ suppression and familial retinoblastoma (4). Nonetheless, the pathogenesis of SC is not yet completely understood. Mutational inactivation of p53 may be pathogenetically relevant in MTS-associated SC and sporadic cases (5, 6). Immunohistochemical analyses have demonstrated that proteins involved in angiogenesis, cell proliferation and inflammation, such as epidermal growth factor receptor (7) and vascular endothelial growth factor receptor (VEGFR) (8), are overexpressed in SC and may play a role in its pathogenesis. To the best of our knowledge, this is the first study analysing the expression of proteins related to angioge- nesis in ocular and extraocular SC using a broad panel of immunohistochemical markers, including D2-40 (po- doplanin), vascular endothelial growth factor (VEGF), VEGFR-2 (KDR) and VEGFR-3 (FLT4). These proteins may not only contribute to the pathogenesis of SC but also act as potential therapeutic targets. MATERIALS AND METHODS Specimens A total of 40 SC cases, including 18 ocular (female/male: 9/9) and 22 extraocular (female/male: 14/8) cases, were analysed This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.