Publications by authors named "Hadaschik E"

Article Synopsis
  • Researchers studied patients with advanced skin cancer (melanoma) to see how well they responded to a special treatment called immune checkpoint inhibition (ICI).
  • They found that only about 8% of patients responded quickly to the treatment, while others had slower responses or did not respond at all.
  • Despite the quick responders showing some improvement, they didn’t live longer or have better outcomes than those who responded later to the treatment.
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Background: Melanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as "triple wild-type" (tWT) melanomas. They constitute 5-10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date.

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Article Synopsis
  • Screening for gene mutations in melanoma has become standard practice, with identified mutations impacting prognosis in metastatic uveal melanoma, while their significance in non-uveal melanoma is still unclear.
  • A study analyzing 2,650 melanoma cases found mutations in 129 samples, highlighting differences in the prevalence and types of mutations between uveal and non-uveal melanomas.
  • Unlike uveal melanomas, where mutations are linked to worse outcomes, mutations in non-uveal melanomas are mostly seen as "passenger mutations" with little impact on prognosis or treatment effectiveness.
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Melanoma causes the majority of skin cancer-related deaths. Despite novel therapy options, metastatic melanoma still has a poor prognosis. Immune checkpoint inhibition (ICI) therapy has been shown to prolong overall survival in patients with advanced melanoma, but mucosal melanomas respond less favorably compared to melanomas of cutaneous origin.

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Article Synopsis
  • * These tumors can be aggressive, often recurring and metastasizing, especially periocular ones (up to 15%), while extraocular cases have a lower metastasis rate (up to 2%).
  • * The main treatment is complete micrographically controlled surgery, with additional options like radiotherapy, while advanced cases may require individualized treatment plans from a tumor board due to a lack of standard therapies.
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Background: Cutaneous adnexal tumors are a diverse group of tumors arising from structures of the hair appendages. Although often benign, malignant entities occur which can metastasize and lead to patients´ death. Correct diagnosis is critical to ensure optimal treatment and best possible patient outcome.

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Introduction: Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA).

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Background: Institutes of dermatopathology are faced with considerable challenges including a continuously rising numbers of submitted specimens and a shortage of specialized health care practitioners. Basal cell carcinoma (BCC) is one of the most common tumors in the fair-skinned western population and represents a major part of samples submitted for histological evaluation. Digitalizing glass slides has enabled the application of artificial intelligence (AI)-based procedures.

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Article Synopsis
  • PD-1-based immune checkpoint inhibitors are key treatments for melanoma, and tumor PD-L1 expression is a crucial biomarker for predicting therapy success.
  • This study analyzed PD-L1 levels from various tumor tissues, including primary tumors and metastases, from 448 patients who received treatment between 2014 and 2020, comparing their correlation with treatment outcomes like best overall response and survival rates.
  • Results showed that PD-L1 positivity in lymph node metastases was significantly associated with better treatment responses and overall survival, while primary tumors and skin/subcutaneous metastases showed weaker correlations.
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Background: In melanoma patients, surgical excision of the first draining lymph node, the sentinel lymph node (SLN), is a routine procedure to evaluate lymphogenic metastases. Metastasis detection by histopathological analysis assesses multiple tissue levels with hematoxylin and eosin and immunohistochemically stained glass slides. Considering the amount of tissue to analyze, the detection of metastasis can be highly time-consuming for pathologists.

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Purpose: Recent studies have demonstrated HLA class II (HLA-II)-dependent killing of melanoma cells by cytotoxic CD4 T cells. We investigated evolution of HLA-II-loss tumors that escape cytotoxic CD4 T-cell activity and contribute to immunotherapy resistance.

Experimental Design: Melanoma cells from longitudinal metastases were studied for constitutive and IFN-inducible HLA-II expression, sensitivity towards autologous CD4 T cells, and immune evasion by HLA-II loss.

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Purpose: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.

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Background: Immune responses against tumors are subject to negative feedback regulation. Immune checkpoint inhibitors (ICIs) blocking Programmed cell death protein 1 (PD-1), a receptor expressed on T cells, or its ligand PD-L1 have significantly improved the treatment of cancer, in particular malignant melanoma. Nevertheless, responses and durability are variables, suggesting that additional critical negative feedback mechanisms exist and need to be targeted to improve therapeutic efficacy.

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Background: The COVID-19 lockdown had a dramatic impact on primary care access and resulted in postponed skin cancer screenings. This raises concerns for a diagnostic delay on primary cutaneous melanomas, which can subsequently increase morbidity and mortality.

Objectives: The aim of the study was to investigate the impact of the COVID-19-related restrictions on the melanoma diagnosis in five European skin cancer reference centres in Switzerland, Germany, Austria and Italy.

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Background: Activating hot spot R29S mutations in RAC1, a small GTPase influencing several cellular processes including cell proliferation and cytoskeleton rearrangement, have been reported in up to 9% of sun-exposed melanomas. Clinical characteristics and treatment implications of RAC1 mutations in melanoma remain unclear.

Methods: We investigated the largest set (n = 64) of RAC1 mutated melanoma patients reported to date, including a retrospective single institution cohort (n = 34) from the University Hospital Essen and a prospective multicentre cohort (n = 30) from the translational study Tissue Registry in Melanoma (TRIM; CA209-578), for patient and tumour characteristics as well as therapy outcomes.

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Mucous membrane pemphigoid (MMP) is a pemphigoid disease with predominant mucous membrane involvement. It mainly affects the mucous membranes of the mouth, eyes, nose and pharynx, but also the larynx, trachea, esophagus, genital and perianal regions. The manifestation of the disease covers a wide spectrum from gingival erythema and single oral lesions to severe tracheal strictures that obstruct breathing and conjunctival scarring with marked visual impairment and, not infrequently, blindness.

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Leukocyte adhesion deficiency type 1 (LAD-1) is a rare disease resulting from mutations in the gene encoding for the common β-chain of the β2-integrin family (CD18). The most prominent clinical symptoms are profound leukocytosis and high susceptibility to infections. Patients with LAD-1 are prone to develop autoimmune diseases, but the molecular and cellular mechanisms that result in coexisting immunodeficiency and autoimmunity are still unresolved.

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Melanocytic neoplasms have been genetically characterized in detail during the last decade. Recurrent exon 3 mutations have been recognized in the distinct group of melanocytic tumors showing deep penetrating nevus-like morphology. In addition, they have been identified in 1-2% of advanced melanoma.

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