This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).

Nestin is an intermediate filament expressed in proliferating neural progenitor cells and has been considered as a stem cell marker. Nestin is also found in melanoma and we recently demonstrated that its expression in melanoma cell lines is regulated by the transcription factors SOX9 and SOX10, but not BRN2. In this study, the expression levels of nestin, BRN2, SOX9 and SOX10 were analysed in tissues of melanoma (n = 78) and melanocytic nevi (n = 26) by immunohistochemistry. All proteins were highly expressed in primary and metastatic melanomas and, apart from BRN2, showed much lower levels in melanocytic nevi. Significant coexpression of nestin with SOX9 and SOX10 was found in primary melanoma confirming our in vitro data.Correlation analysis with clinicopathological data revealed that nestin was significantly associated with presence of ulceration in primary tumors and SOX9 with more advanced stage of disease. Our data reveal that SOX9 and SOX10 are highly expressed in melanoma and seem to have a regulatory role in nestin expression. The association with ulceration and advanced-stage tumors, respectively, suggests that nestin and SOX9 may be negative prognostic markers in melanoma.

A single nucleotide polymorphism in the gene for FGFR4 (ÀArg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P ¼ 0.023 and AJCC, P ¼ 0.046), presence of microulceration (P ¼ 0.009), tumour vascularity (P ¼ 0.001), metastases (P ¼ 0.025), number of primary tumours (P ¼ 0.022), overall survival (P ¼ 0.047) and disease-free survival (P ¼ 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P ¼ 0.004) and by Breslow in mm (P ¼ 0.02)) and the tumour subtype nodular melanoma (P ¼ 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.

StatementDie Behandlungsstrategien basieren auf der exakten Diagnose, den Vorbehandlungen und auf dem Erkrankungsstadium.Konsensus: 100 % EmpfehlungenDie Therapie der MF soll entsprechend den in Tabelle 1 gelisteten Empfehlungen erfolgen. Konsensus: 100 % Die Therapie des Sézary-Syndroms soll entsprechend den in Tabelle 2 gelisteten Empfehlungen erfolgen. Konsensus: 86 % Die Therapie der CD30+ lymphoproliferativen Erkrankungen der Haut soll entsprechend den in Tabelle 3 gelisteten Empfehlungen erfolgen. Konsensus: 100 % Die Therapie der kutanen B Zell-Lymphome soll entsprechend den Tabellen 4a und 4b gelisteten Empfehlungen erfolgen. Konsensus: 100 %

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