Mesenchymal-epithelial transition in lymph node metastases of oral squamous cell carcinoma is accompanied by ZEB1 expression.

Background: Oral squamous cell carcinoma (OSCC), an HPV-negative head and neck cancer, frequently metastasizes to the regional lymph nodes but only occasionally beyond. Initial phases of metastasis are associated with an epithelial-mesenchymal transition (EMT), while the consolidation phase is associated with mesenchymal-epithelial transition (MET). This dynamic is referred to as epithelial-mesenchymal plasticity (EMP).

Phenotypic plasticity of malignant T cells in blood and skin of a Sézary syndrome patient revealed by single cell transcriptomics.

Background: Sézary Syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL). In SS patients, malignant T cells are circulating through the blood and cause erythroderma.

Objective: To compare the transcriptome of single cells in blood and skin samples from a patient with advanced SS.

Structure and dynamics of the von Willebrand Factor C6 domain.

Von Willebrand disease (VWD) is a bleeding disorder with different levels of severity. VWD-associated mutations are located in the von Willebrand factor (VWF) gene, coding for the large multidomain plasma protein VWF with essential roles in hemostasis and thrombosis. On the one hand, a variety of mutations in the C-domains of VWF are associated with increased bleeding upon vascular injury.

Undifferentiated pleomorphic sarcoma of the breast with neoplastic fever: case report and genomic characterization.

Purpose: Primary breast sarcomas are extraordinary rare, in particular undifferentiated pleomorphic sarcoma (UPS). UPS with neoplastic fever (UPS-NF) of the breast has not been reported yet. Here, we present an extended UPS-NF of the breast including its comprehensive molecular workup.

Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma.

Background: Based on its viral-associated or UV-associated carcinogenesis, Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Thus, clinically evident MCC occurs either in immuno-compromised patients or based on tumor-intrinsic immune escape mechanisms. This notion may explain that although advanced MCC can be effectively restrained by treatment with PD-1/PD-L1 immune checkpoint inhibitors (ICIs), a considerable percentage of patients does not benefit from ICI therapy.

Genetic analysis of single disseminated tumor cells in the lymph nodes and bone marrow of patients with head and neck squamous cell carcinoma.

Considering the limited information on the biology and molecular characteristics of disseminated tumor cells (DTCs) in head and neck squamous cell carcinoma (HNSCC), we examined the genomic alterations in DTCs from HNSCCs and their potential clinical relevance. To analyze both the lymphatic and hematogenous routes of tumor cell dissemination, we investigated samples from lymph nodes (LNs) and bone marrow (BM) of 49 patients using immunofluorescence double staining for epithelial cells expressing cytokeratin 18 (KRT18) and/or epithelial cell adhesion molecules (EpCAM, CD326). The identified marker-positive cells were isolated by micromanipulation followed by single-cell whole-genome amplification and metaphase-based comparative genomic hybridization (mCGH) to determine genome-wide copy number alterations.

Comparison of mutation profiles in primary melanomas and corresponding nodal naevi using next-generation sequencing.

Background: Nodal naevi (NN) represent aggregates of melanocytes within peripheral lymph nodes. NN are relatively often found in patients with malignant melanoma (MM), and may mimic metastatic disease.

Aim: To study mutation profiles in MM and NN to find out whether NN descend from a primary MM.

Classical and Variant Merkel Cell Carcinoma Cell Lines Display Different Degrees of Neuroendocrine Differentiation and Epithelial-Mesenchymal Transition.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer characterized by high invasiveness, early metastases, and high mortality. Because of the lack of suitable animal models, most functional studies are performed using cell lines, some of which lack classical neuroendocrine growth characteristics. Here, we scrutinized the molecular characteristics of classical MCC and variant MCC cell lines by differential gene expression and the respective epigenetic regulation by microRNAs and DNA methylation.

Mutational Landscape of Virus- and UV-Associated Merkel Cell Carcinoma Cell Lines Is Comparable to Tumor Tissue.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy that is either associated with the integration of the Merkel cell polyomavirus or chronic UV exposure. These two types of carcinogenesis are reflected in characteristic mutational features present in MCC tumor lesions. However, the genomic characteristics of MCC cell lines used as preclinical models are not well established.

Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53.

Merkel cell carcinoma (MCC) is a highly invasive and metastatic skin cancer. While high expression of miR-375 is a characteristic of MCC, it seems not to contribute to the malignant phenotype of MCC cells. miR-375 enrichment in MCC-derived extracellular vesicles suggests its intercellular signaling function.

Highly Expressed miR-375 is not an Intracellular Oncogene in Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma.

miR-375 is a highly abundant miRNA in Merkel cell carcinoma (MCC). In other cancers, it acts as either a tumor suppressor or oncogene. While free-circulating miR-375 serves as a surrogate marker for tumor burden in patients with advanced MCC, its function within MCC cells has not been established.

Elevated baseline serum PD-1 or PD-L1 predicts poor outcome of PD-1 inhibition therapy in metastatic melanoma.

Background: Programmed cell death protein 1 (PD-1) checkpoint inhibition has recently advanced to one of the most effective treatment strategies in melanoma. Nevertheless, a considerable proportion of patients show upfront therapy resistance and baseline predictive biomarkers of treatment outcome are scarce. In this study we quantified PD-1 and programmed death-ligand 1 (PD-L1) in baseline sera from melanoma patients in relation to therapy response and survival.