MicroRNAs (miRNAs) are small noncoding RNAs (∼22 bp) that posttranscriptionally regulate gene expression. MiRNAs possess oncogenic or tumor suppressor activity in various tumors but little is known about miRNA expression pattern in malignant melanoma. We determined the expression level of 16 potentially relevant miRNAs (miR‐15a, miR‐15b, miR‐16, miR‐34a, miR‐210, let‐7I, miR‐23a, miR‐23b, miR‐24, miR‐27a, miR‐27b, miR‐100, miR‐137, miR‐222, miR‐373‐1, miR‐373*) by real‐time PCR in 6 preparations of normal melanocytes vs. 10 melanoma cell lines and in formalin fixed paraffin embedded tissue of 11 melanocytic nevi versus 16 melanomas. MiR‐15b and miR‐210 were significantly upregulated, miR‐34a was significantly downregulated in melanomas compared with melanocytic nevi. These 3 miRNAs were analyzed in a total of 128 primary melanomas from patients with detailed clinical follow‐up information. High expression of miR‐15b (but not miR‐210 upregulation and miR‐34a downregulation) was significantly associated with poor recurrence free survival and overall survival by univariate Kaplan‐Meier and multivariate Cox analyses. Downregulation of miR‐15b in two melanoma cell lines with high miR‐15b expression by transfection with anti‐miR‐15b siRNA was associated with reduced tumor cell proliferation, whereas apoptosis was increased. In summary, miRNA expression levels show distinct differences comparing benign and malignant melanocytic cell proliferations and can provide independent prognostic informations. MiR‐15b appears to represent a particular important miRNA in melanoma that is associated with poor prognosis and tumorigenesis.

Recent data suggested an increased frequency of KIT aberrations in mucosal melanomas, whereas c-KIT in most types of cutaneous melanomas does not appear to be of pathogenetic importance. However, studies investigating the status of the KIT gene in larger, well-characterised groups of patients with mucosal melanomas are lacking. We analysed 44 archival specimens of 39 wellcharacterised patients with mucosal melanomas of different locations. c-KIT protein expression was determined by immunhistochemistry, KIT gene mutations were analysed by PCR amplification and DNA sequencing of exons 9, 11, 13, 17 and 18. c-KIT protein expression could be shown in 40 out of 44 (91%) tumours in at least 10% of tumour cells. DNA sequence analysis of the KIT was successfully performed in 37 patients. In 6 out of 37 patients (16%) KIT mutations were found, five in exon 11 and one in exon 18. The presence of mutations in exon 11 correlated with a significant stronger immunohistochemical expression of c-KIT protein (P ¼ 0.015). Among the six patients with mutations, in two patients the primary tumour was located in the head/neck region, in three patients in the genitourinary tract and in one patient in the anal/rectal area. In conclusion, KIT mutations can be found in a subset of patients with mucosal melanomas irrespective of the location of the primary tumour. Our data encourage therapeutic attempts with tyrosine kinase inhibitors blocking c-KIT in these patients. British Journal of Cancer (2008) (Chang et al, 1998) and have mainly been described in the head and neck region, the genitourinary tract and the gastrointestinal tract.Obviously, sun exposure does not play a role in mucosal melanoma, whereas it is a risk factor in cutaneous melanoma. A recent study described genetic differences between mucosal melanomas and cutaneous melanomas. In this study, four types of melanomas were differentiated, that is, mucosal melanomas, acral melanomas, melanomas on skin with chronic sun damage and melanomas on skin without chronic sun damage. Melanomas arising from skin without chronic sun damage, representing the major group of cutaneous melanomas, were shown to frequently harbour BRAF mutations, in particular the BRAF V600E mutation. The other melanoma types, including mucosal melanoma, had a high frequency of mutations of the KIT gene (Curtin et al, 2005(Curtin et al, , 2006. This finding is in particular intriguing as it may represent a rationale for a targeted therapy with specific tyrosine kinase inhibitors such as c-KIT blockers in mucosal melanomas. To further elucidate the role of c-KIT and BRAF in mucosal melanoma, we analysed these two targets in 39 patients with mucosal melanomas treated in our Department. MATERIALS AND METHODS PatientsThirty nine patients with mucosal melanomas who were treated in our Department (Skin Cancer Center Hannover) from 1996 to 2007 were retrospectively analysed. A total of 44 archival formalin-fixed and paraffin-embedded tissue samples (35 primary melanomas, 4 lymph node metastases, 2 skin metastases and ...

The multikinase inhibitor sorafenib is therapeutically used in various malignancies. Multiple cutaneous side effects are well described but recent reports indicated a possible association of epithelial skin cancer growth during sorafenib therapy. To our knowledge, few cases of actinic keratoses and variants of squamous cell carcinomas associated with sorafenib have been published. We report 2 patients who developed a basal cell carcinoma (BCC) while treated with sorafenib. Interestingly BCC is a tumor which has not been described yet in association with sorafenib therapy. The tumors were excised completely. After termination of sorafenib treatment, no new BCCs or other epithelial skin cancers occurred. There is accumulating evidence in the literature that sorafenib and possibly other targeted agents are associated with an increased occurrence of epithelial skin cancers. These observations are summarized here and complemented by the new observation that al- so BCCs might be associated with sorafenib therapy. The pathogenetic mechanisms are unclear so far but induction of the mitogen-activated protein kinase pathway in wild-type RAF cells by RAF inhibitors might play a role. Patients should be informed of this possible side effect and undergo regular dermatological controls before and during sorafenib therapy.

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