Kurt Werner Schmid

Kurt Werner Schmid
University of Duisburg-Essen | uni-due · Institute of Pathology

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818
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Introduction
Skills and Expertise

Publications

Publications (818)
Article
Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional...
Article
Purpose: Restoration of iodine incorporation (redifferentiation) by mitogen-activated protein kinase (MAPK) inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant RR-TC. Here we assess safety and efficacy of redifferentiation therapy through gen...
Article
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Background: Malignant pleural mesothelioma (MPM) has an infaust prognosis due to resistance to systemic treatment with platin-analoga. MPM cells modulate the immune response to their benefit. They release proinflammatory cytokines, such as TGF-ß, awakening resting fibrocytes that switch their phenotype into activated fibroblasts. Signaling interac...
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Background High-grade serous ovarian cancer (HGSOC) is the predominant and deadliest form of ovarian cancer. Some of its histological subtypes can be distinguished by frequent occurrence of cancer-associated myofibroblasts (CAFs) and desmoplastic stroma reaction (DSR). In this study, we want to explore the relationship between therapy outcome and t...
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Background Autopsies are an important tool in medicine, dissecting disease pathophysiology and causes of death. In COVID-19, autopsies revealed e.g., the effects on pulmonary (micro)vasculature or the nervous system, systemic viral spread, or the interplay with the immune system. To facilitate multicentre autopsy-based studies and provide a central...
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Background Immune checkpoint inhibitors (ICIs) are currently one of the most promising therapy options in the field of oncology. Although the first pivotal ICI trial results were published in 2011, few biomarkers exist to predict their therapy outcome. PD-L1 expression and tumor mutational burden (TMB) were proven to be sometimes-unreliable biomark...
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Purpose The role of streptozocin-based chemotherapy (STZ CTx) in advanced, well-differentiated pancreatic neuroendocrine tumours (PanNET) and the best sequence of treatments in advanced PanNET are unclear. We examined the outcomes after STZ CTx in patients who had been selected according to the current therapeutic guidelines. Methods Data from 50...
Article
Background Predictive criteria to determine the absence of node metastases from thyroid specimens are scarce for sporadic medullary thyroid cancer. Methods Histopathologic stratification of patients with unifocal sporadic medullary thyroid cancer ≤25 mm with ≥10 neck nodes at thyroidectomy to evaluate the suitability of desmoplasia (7 increments)...
Article
Introduction: Primary squamous cell carcinoma (PSCC) of the thyroid is an exceptionally rare malignancy accounting for <1% of all primary thyroid cancers. Therapy is multimodal including surgery, radiotherapy, and chemotherapy but with no consensus for management and therapy. Here, we describe a case of a male patient who presented with a BRAF V60...
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Background The tyrosine kinase inhibitors (TKI) vandetanib and cabozantinib are approved as targeted therapies in advanced medullary thyroid carcinoma (MTC) with symptoms or high tumour burden. Only recently, toxicity in long-time TKI usage was analysed. However, little is known about the impact of TKI discontinuation on MTC disease course after lo...
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Aims In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. Methods D...
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Background Gastritis induced by checkpoint inhibitors (CPI) is a rare but severe drug-related side effect. The reference standard for confirming CPI-associated gastritis (CPI-assGastritis) is histopathological assessment; however, the histopathological features of CPI-assGastritis are not yet adequately defined.Materials and Methods Gastric biopsie...
Article
Background: Malignant pleural mesothelioma (MPM) is a rare malignant tumor associated with asbestos exposure, with infaust prognosis and overall survival below 20 months in treated patients. Platinum is still the backbone of the chemotherapy protocols, and the reasons for the rather poor efficacy of platinum compounds in MPM remain largely unknown...
Article
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Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with asbestos exposure. Median survival ranges from 14 to 20 months after initial diagnosis. As of November 2020, the FDA approved a combination of immune checkpoint inhibitors after promising intermediate results. Nonetheless, responses remain unsatisfying. Adequate patien...
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Cystic echinococcosis is a widely endemic helminthic disease worldwide but occurs only rarely in Central Europe. Humans are infected as ‘aberrant’ hosts by Echinococcus granulosus and develop cysts in numerous different organs. 20%–30% of the affected individuals develop hydatid disease in the lungs with associated complications including pleuritis...
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Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbour somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been i...
Article
The current edition of the WHO classification of thyroid tumors (2017) contains a number of very relevant changes with considerable consequences for the diagnostic assessment of thyroid specimens. This applies to both the histomorphological examination of surgical specimens and the preoperative fine needle biopsy (FNB). In addition, molecular patho...
Article
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Malignant pleural mesothelioma (MPM) is a rare, but aggressive tumor with dismal prognosis. Platinum-based chemotherapy is regularly used as part of multimodality therapy. The expression of metallothioneins (MT) has been identified as a reason for cisplatin resistance, which often leads to early therapy failure or relapse. Thus, knockdown of MT exp...
Article
Murine models of myeloid neoplasia show how leukemia infiltration alters the hematopoietic stem cell (HSC) niche to reinforce malignancy at the expense of healthy hematopoiesis. However, little is known about the bone marrow architecture in humans and its impact on clinical outcome. Here, we dissect the bone marrow niche in patients with acute myel...
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Nuclear inclusions (NI) are a common finding in hepatocytes from patients with liver disease especially in diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) but studies examining the shape and content of these inclusions in detail are lacking. In this study we define two distinct types of NI in NAFLD: inclusions bounded by the nuclear...
Article
We report the case of a 70-year-old female patient with an unclear liver mass after clinical and radiological evaluation. In histopathological evaluation, we diagnosed a hepatic angiomyolipoma, which is a rare entity and belongs to the perivascular epithelioid group of tumours (PEComa). In this report, we illustrate the typical histomorphology, imm...
Article
Introduction: Urachal cancer (UrC) is a rare but aggressive cancer. Due to its low incidence, structured epidemiological data have only rarely been reported. To date, no valid data on UrC are available for the German population. Methods: Data on incidence and relative 5-year survival of urachal lesions (ICD-10: C67.7) were collected from all pop...
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In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.
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Aim: β-catenin activation is known to promote liver regeneration and play a role in the pathogenesis of liver cancer. Recently, we detected intranuclear inclusions (NI) in hepatocellular carcinoma (HCC) containing degenerated cell organelles and lysosomal proteins and delimited by a completely closed nuclear membrane. The presence of NI was positiv...
Article
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Background: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor associated with a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons underlying the rather poor efficacy of platinum compounds remain largely unknown...
Article
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Clostridium perfringens enterotoxin (CPE) can be used to eliminate carcinoma cells that overexpress on their cell surface CPE receptors – a subset of claudins (e.g. Cldn3 and Cldn4). However, CPE cannot target tumors expressing solely CPE‐insensitive claudins (such as Cldn1 and Cldn5). To overcome this limitation, structure‐guided modifications wer...
Article
Es wird ein Fall ektopen Schilddrüsengewebes in der Nebenniere präsentiert und Entstehungskonzepte dieser Entität diskutiert. Subdiaphragmal lokalisiertes ektopes Schilddrüsengewebe ist äußerst selten und die potentiellen Entstehungsmechanismen komplexer und schwieriger nachvollziehbar als die des häufiger auftretenden ektopen Gewebes entlang des e...
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Purpose: Response to platinum-based therapy is a major prognostic factor in high-grade serous ovarian cancer (HGSOC). While the exact mechanisms of platinum-resistance remain unclear, evidence is accumulating for a connection between the organism's immune-response and response to platinum. However, predictive tools are missing. This study was perf...
Poster
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The protein Gsα encoded by GNAS is a key player in pathways relevant for tumour growth, progression or metastatic spread. In a previous comprehensive meta-analysis, we could show for ten different cancer entities that the synonymous germline single nucleotide polymorphism (SNP) rs7121 (c.393C>T) is associated with shorter overall, progression-free...
Poster
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Background: Malignant pleural mesothelioma (MPM) is a tumour with dismal prognosis. Chemotherapeutic treatment with pemetrexed combined with cisplatin shows unsatisfying response-rates of 40%. The reasons for the rather poor efficacy remain largely unknown. However, it is conceivable that DNA repair mechanisms lead to an impaired therapy response....
Poster
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Immune checkpoint inhibition uses monoclonal antibodies targeting major regulators of the immune response. PD-1 and PD-L1 targeting has become one of the most thriving therapeutic approaches in modern oncology. Unfortunately, 60-80% of all patients will develop long-term resistances under immunotherapy. Hence, we have theorized altered proteasomal...
Article
Introduction Ovarian carcinoma is associated with the highest mortality of all gynecologic malignancies. Even after optimal treatment, prognosis remains poor. There is no established biomarker to predict individual patient outcome. Objective To evaluate the prognostic significance of PD-1 and PD-L1 expression in tumor tissues from patients with ov...
Article
Zusammenfassung Die morphologische Diagnostik von Schilddrüsentumoren dient in erster Linie dem klinischen Management. Die Feinnadelbiopsie (FNB) soll eine Entscheidungshilfe für oder gegen eine Operation sein; der intraoperative Gefrierschnitt soll das Operationsausmaß mitbestimmen und Zweitoperationen vermeiden helfen. Die beiden letztgenannten M...
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Background: Bortezomib is an approved proteasome inhibitor for the treatment of certain lymphoma subtypes. Two clinical trials investigated bortezomib in patients with malignant pleural mesothelioma (MPM) and failed to improve outcome. We present a potential explanation for this event. Methods: 171 patients with MPM were analyzed for their mRNA...
Poster
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Introduction: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor leading to a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. Platin-compounds resulted in a response rate of merely 6-14% and a median survival of below 7 mo...
Presentation
Background: A modern foundation of cancer treatment is immune checkpoint inhibition, which is supposed to increase the tumors susceptibility towards the patient’s immune system. However, up to 60% of patients with long-term treatment face therapy resistance. In previous works, we found hints of an immune escape mechanism in association with altere...
Poster
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G-protein coupled receptors play a key role in multiple signal transduction pathways. Altered activity of the stimulatory Gsα subunit, which is encoded by the gene GNAS, is associated with tumour growth, angiogenesis or metastatic spread. GNAS sequence alterations and conformity changes of the Gsα protein could enhance or diminish the function of G...
Article
G-protein receptor signaling plays a key role in multiple signal transduction pathways. Aberrant activity of the stimulatory Gsα subunit has been frequently associated with cancer. GNAS sequence alterations and conformational changes of Gsα can both enhance or diminish its function and change downstream effects of G-protein receptor signaling. In t...
Article
Background Anaplastic thyroid cancer (ATC) is a very rare malignancy and accounts for 2–5% of all thyroid cancers. It represents one of the most aggressive human malignancies. This review aims to provide a brief update on the epidemiology, molecular pathology and treatment strategies for ATC. Results Distant metastases are a frequent finding at th...
Article
Full-text available
For decades, intranuclear inclusions in many normal and neoplastic cells have been considered to be mere invaginations of cytoplasm into the nucleus without any notable function or influence on disease. We investigated such inclusions in 75 specimens of hepatocellular carcinoma (HCC). In this context we demonstrate that these inclusions are true in...
Article
Thyroid hormones are important for physiology and homeostasis. In addition to nuclear thyroid hormone receptors, the plasma membrane protein integrin αvβ3 has been recognized as a receptor for both thyroxine (T4) and triiodothyronine (T3). Here, we studied whether thyroid hormone promotes growth of murine lung cancer via αvβ3 in vivo. Murine Lewis...
Article
Full-text available
Background Malignant pleural mesothelioma (MPM) is a tumour arising from pleural cavities with poor prognosis. Multimodality treatment with pemetrexed combined with cisplatin shows unsatisfying response-rates of 40%. The reasons for the rather poor efficacy of chemotherapeutic treatment are largely unknown. However, it is conceivable that DNA repai...
Article
Introduction: The usage of formalin-fixed paraffin embedded (FFPE) tissue is characterized by its long shelf-life and simple handling. Therefore it is the most commonly available tissue specimen in routine diagnostics and histological studies. Formaldehyde fixation may result in RNA degradation and cross linking with proteins, while storage conditi...
Article
The hematopoietic stem cell (HSC) niche consists of different cellular and non-cellular constituents which regulate HSC maintenance and retention in the bone marrow. It has been shown in a number of murine models of myeloid neoplasia how leukemia infiltration alters the HSC niche to reinforce malignancy. Acute myeloid leukemia (AML) is characterize...
Poster
Background: Malignant pleural mesothelioma (MPM) is a rare, but aggressive tumor with dismal prognosis. Platinum-based chemotherapy is often used as part of multimodal therapy. Metallothioneins (MT) are a possible reason for cisplatin resistance, which often leads to early therapy failure or relapse. Methods: The MT gene- and protein-expression o...
Article
Full-text available
Background Malignant pleural mesothelioma (MPM) is a biologically highly aggressive tumor arising from the pleura with a dismal prognosis. Cisplatin is the drug of choice for the treatment of MPM, and carboplatin seems to have comparable efficacy. Nevertheless, cisplatin treatment results in a response rate of merely 14% and a median survival of le...
Article
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provi...
Article
Background Deregulation of signal transduction pathways plays a critical role in oncogenesis of colorectal cancer (CRC) and directly impacts on sensitivity to targeted therapies. Against this background we developed a comprehensive biomarker profiling program including markers of downstream signaling to study their association with clinical outcome...
Chapter
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This chapter presents the results of studies on pediatric papillary thyroid carcinoma (PTC) in Belarus after the Chernobyl accident. Our investigations are based on a scrupulous histopathological review of all cases by a group of experienced pathologists with special skills in thyroid neoplasia, who confirmed the diagnosis, and determined the exten...
Poster
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Background: Desmoplastic stromal reactions are a well-known phenomenon occurring in many different types of tumors, the underlying molecular mechanisms are not fully understood. However, their suitability as prognostic marker is controversially discussed. Methods: We analyzed three different kinds of tumors (thyroid, ovarian, breast cancers) with a...
Poster
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Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor arising from pleural cavities with poor prognosis. The remission-rate during the most effective chemotherapeutical regimen of pemetrexed combined with cisplatin is only about 40%. The reasons for the rather poor efficacy remain largely unknown. However, it is likely tha...
Article
Full-text available
PurposeTo evaluate the impact of three BCL2 single-nucleotide polymorphisms, i.e., c.−938C>A (rs2279115), c.21G>A (rs1801018), and c.*2203A>G (rs4987853) on survival in patients with transitional cell carcinoma of the bladder. Methods We analyzed 179 patients who underwent surgical treatment for bladder cancer at the Clinic of Urology, University H...
Article
Zusammenfassung Schilddrüsenknoten stellen heterogene Tumore dar, mit unterschiedlichen molekularen Signaturen. Während benigne Schilddrüsenknoten poly- oder monoklonalen Tumoren entsprechen, sind Schilddrüsenkarzinome monoklonale und damit „echte“ Neoplasien. Ursächlich für die Neoplasien sind somatische Mutationen, welche zur konstitutiven Aktivi...
Article
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PurposeThe therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its...
Article
Background: Tumor infiltrating lymphocytes (TILs) are described as an important immune modulator in the tumor microenvironment in cancer and were shown to be associated with breast cancer (BC) outcome. Besides the analysis of total TILs, the discrimination into TIL subtypes is essential as they exhibit pro- or anti-tumorigenic potential. The spatio...
Poster
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Background: Lung cancer is the leading cause of cancer-related deaths worldwide. The typical and atypical carcinoid (TC and AC), the large-cell neuroendocrine carcinoma (LCNEC) and the small-cell lung cancers (SCLC) are subgroups of pulmonary tumors that show neuroendocrine differentiations (NELC). With the rising impact of molecular pathology in r...