Melanoma in association with a nevus in overview (A) and closeup (B).

<p>Immunohistochemically stained in (C) with the BRAF^V600E-mutation specific antibody VE1. Benign(D) and malignant(F) parts of the tumor in closeup. E&G show sequencing result of the corresponding cuts.</p

Representative tumor parts of nevi groups.

<p>Melanoma associated nevi are more commonly strictly dermal and show less of the postulated features of so called "dysplastic" nevi.</p

NRAS and BRAF Mutations in Melanoma-Associated Nevi and Uninvolved Nevi

<div><p>According to the prevailing multistep model of melanoma development, oncogenic BRAF or NRAS mutations are crucial initial events in melanoma development. It is not known whether melanocytic nevi that are found in association with a melanoma are more likely to carry BRAF or NRAS mutations than uninvolved nevi. By laser microdissection we were able to selectively dissect and genotype cells either from the nevus or from the melanoma part of 46 melanomas that developed in association with a nevus. In 25 cases we also genotyped a control nevus of the same patients. Available tissue was also immunostained using the BRAF^V600E-mutation specific antibody VE1. The BRAF^V600E mutation was found in 63.0% of melanomas, 65.2% of associated nevi and 50.0% of control nevi. No significant differences in the distribution of BRAF or NRAS mutations could be found between melanoma and associated nevi or between melanoma associated nevi and control nevi. In concordant cases immunohistochemistry showed a higher expression (intensity of immunohistochemistry) of the mutated BRAF^V600E-protein in melanomas compared to their associated nevi. In this series the presence of a BRAF- or NRAS mutation in a nevus was not associated with the risk of malignant transformation. Our findings do not support the current traditional model of stepwise tumor progression.</p> </div

Visualization 4: In vivo dual-modality photoacoustic and optical coherence tomography imaging of human dermatological pathologies

3D-rendered video of fused PAT/OCT data of a patient with chronic hyperkeratotic hand eczema with a virtual cutout depicting the surface of the epidermis, a part of the capillary loop system, and the papillary dermis. The OCT data is presented with t Originally published in Biomedical Optics Express on 01 September 2015 (boe-6-9-3163

Comparison of mutation status between paired tumor groups.

<p>BRAF^V600E-mutation status was evaluated by VE1-Immunohistochemistry and Sanger sequencing, NRAS^Q61 by Sanger sequencing alone. p-values denote two-tailed significance as measured by McNemar test.</p

Multivariate Cox regression analysis of risk factors associated with progression-free and overall survival.

<p>A) Risk factors associated with progression-free survival (multivariate Cox regression analysis) B) Risk factors associated with overall survival (multivariate Cox regression analysis).</p

Functional Classification of Cellular Proteome Profiles Support the Identification of Drug Resistance Signatures in Melanoma Cells

Drug resistance is a major obstacle in melanoma treatment. Recognition of specific resistance patterns, the understanding of the patho-physiology of drug resistance, and identification of remaining options for individual melanoma treatment would greatly improve therapeutic success. We performed mass spectrometry-based proteome profiling of A375 melanoma cells and HeLa cells characterized as sensitive to cisplatin in comparison to cisplatin resistant M24met and TMFI melanoma cells. Cells were fractionated into cytoplasm, nuclei and secretome and the proteome profiles classified according to Gene Ontology. The cisplatin resistant cells displayed increased expression of lysosomal as well as Ca²⁺ ion binding and cell adherence proteins. These findings were confirmed using Lysotracker Red staining and cell adhesion assays with a panel of extracellular matrix proteins. To discriminate specific survival proteins, we selected constitutively expressed proteins of resistant M24met cells which were found expressed upon challenging the sensitive A375 cells. Using the CPL/MUW proteome database, the selected lysosomal, cell adherence and survival proteins apparently specifying resistant cells were narrowed down to 47 proteins representing a potential resistance signature. These were tested against our proteomics database comprising more than 200 different cell types/cell states for its predictive power. We provide evidence that this signature enables the automated assignment of resistance features as readout from proteome profiles of any human cell type. Proteome profiling and bioinformatic processing may thus support the understanding of drug resistance mechanism, eventually guiding patient tailored therapy

Distribution of IL28B genotype in study cohort and correlation with expected distribution according to Hardy-Weinberg equilibrium.

<p>Distribution of IL28B genotype in study cohort and correlation with expected distribution according to Hardy-Weinberg equilibrium.</p

Risk factors like sex, age, type of melanoma, tumour thickness and AJCC stage did not differ between CC and non-CC genotype.

<p>Risk factors like sex, age, type of melanoma, tumour thickness and AJCC stage did not differ between CC and non-CC genotype.</p

Baseline characteristics of patients.

<p>Baseline characteristics of patients.</p