Publications by authors named "Till Clauditz"

Background/objectives: Carcinoembryonic antigen (CEA) is a cell-surface glycoprotein serving as a drug target, diagnostic marker, and serum marker for cancer monitoring. However, prevalence data on CEA expression in cancer tissues vary considerably. This study was designed to determine CEA expression in normal and neoplastic tissues.

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Background: Claudin-3 (CLDN3) participates in the formation of the tight-junctions (TJs) that regulate intercellular permeability. Altered CLDN3 expression has been linked to tumor progression in multiple tumor types. Despite its widespread expression in normal epithelial cells, CLDN3 is considered an attractive drug target candidate, since it may be more accessible in cancer cells than in normal cells due to their less orchestrated cell growth.

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PAX6 immunohistochemistry (IHC) was proposed as a tool to identify a pancreatic origin of neuroendocrine neoplasms (NENs). To evaluate the diagnostic utility of PAX6 IHC, a tissue microarray containing 19,214 samples from 150 tumor types was analyzed. Data on progesterone receptor (PR) and glutamate decarboxylase 2 (GAD2) expression were available from previous studies.

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  • Anterior gradient 2 (AGR2) is a key protein involved in various biological processes like embryonic development, tissue regeneration, and wound healing, with potential implications in cancer research.
  • A comprehensive analysis of nearly 15,000 tumors and normal tissue samples revealed that AGR2 expression is present in a majority of tumor categories, particularly in tumors of the female genital tract and various adenocarcinomas.
  • High levels of AGR2 are associated with poor clinical outcomes in several cancer types, suggesting its role as a potential biomarker for tumor aggressiveness and progression.
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The protein gene product 9.5 (PGP9.5), also termed ubiquitin C-terminal hydrolase L1 (UCH-L1) is an important component of the ubiquitination/deubiquitination system and plays a role in axonal transport.

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Background: Head and neck squamous cell carcinoma (HNSCC) negative for Human Papillomavirus (HPV) has remained a difficult to treat entity, whereas tumors positive for HPV are characterized by radiosensitivity and favorable patient outcome. On the cellular level, radiosensitivity is largely governed by the tumor cells` ability to repair radiation-induced DNA double-strand breaks (DSBs), but no biomarker is established that could guide clinical decision making. Therefore, we tested the impact of the expression levels of ATM, the central kinase of the DNA damage response as well as DNA-PKcs and Ku80, two major factors in the main DSB repair pathway non-homologous end joining (NHEJ).

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Trefoil factor 1 (TFF1) plays a role in the mucus barrier. To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). TFF1 staining was detectable in 65 of 149 tumor categories.

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  • TTF-1 immunohistochemistry is commonly used to identify primary pulmonary adenocarcinomas, but it can also appear in various other cancer types.
  • In a study involving 17,772 tumor samples, TTF-1 was found in 82 different tumor categories, indicating a broad range of malignancies where it may be present, spanning from thyroid cancers to neuroendocrine tumors.
  • Although TTF-1 shows high sensitivity for distinguishing pulmonary adenocarcinomas, its specificity is low; combining TTF-1 with Napsin-A significantly enhances diagnostic accuracy.
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  • Loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) is commonly seen in various cancers, making these cells more vulnerable to anti-cancer drugs.
  • A study analyzed over 17,000 tumor samples and found complete MTAP loss in 83 out of 149 tumor types, particularly noting high rates in neuroendocrine tumors and Hodgkin lymphoma.
  • MTAP deficiency is associated with negative tumor characteristics, such as a lack of immune cell infiltration and lower CD8+ lymphocyte density, indicating its potential as a significant diagnostic marker in cancer.
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PAX8 plays a role in development of the thyroid, kidney, and the Wolffian and Mullerian tract. In surgical pathology, PAX8 immunohistochemistry is used to determine tumors of renal and ovarian origin, but data on its expression in other tumors are conflicting. To evaluate PAX8 expression in normal and tumor tissues, a tissue microarray containing 17,386 samples from 149 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

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  • T-lymphocytic intestinal leiomyositis is a rare condition that can lead to pediatric intestinal pseudo-obstructions, making diagnosis challenging.
  • Diagnosis usually requires invasive procedures like full-thickness bowel biopsies via laparotomy or laparoscopy, and treatment currently consists only of immunosuppressive therapy.
  • Early diagnosis and treatment are essential to prevent worsening conditions, and the review highlights a specific case that shows management strategies and compares it to earlier cases in the last two decades.
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Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression in cancer cells is less well characterized, but STING agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for STING by immunohistochemistry.

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Background: Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells.

Methods: To comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

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Background: Early Barrett cancer can be curatively treated by endoscopic resection. The choice of the resection technique, however-endoscopic mucosal resection (EMR) or submucosal dissection (ESD)-largely depends on the assumed infiltration depth as judged by the endoscopist. However, the accuracy of endoscopic diagnosis of the degree of cancer infiltration is not known.

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Objective: There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%-80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD.

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  • * A study analyzed a large tissue microarray and found AR positivity in 116 tumor types, with very high positivity rates in testicular tumors and prostate cancer, but varying degrees in other types like breast and kidney cancers.
  • * Low AR expression was linked to more advanced stages and poorer outcomes in certain cancers like urothelial carcinoma and invasive breast carcinoma, suggesting that AR immunohistochemistry may have limited uses for tumor identification but could be significant in treatment strategies for some cancers.
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EpCAM is expressed in many epithelial tumors and is used for the distinction of malignant mesotheliomas from adenocarcinomas and as a surrogate pan-epithelial marker. A tissue microarray containing 14,832 samples from 120 different tumor categories was analyzed by immunohistochemistry. EpCAM staining was compared with TROP2 and CKpan.

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The Melan-A (melanocyte antigen) protein, also termed 'melanoma antigen recognized by T cells 1' (MART-1) is a protein with unknown function whose expression is specific for the melanocyte lineage. Antibodies against Melan-A are thus used for identifying melanocytic tumors, but some Melan-A antibodies show an additional - diagnostically useful - cross-reactivity against an unspecified protein involved in corticosteroid hormone synthesis. To comprehensively compare the staining patterns of a specific and a cross-reactive Melan-A antibody in normal and neoplastic tissues, tissue microarrays containing 15,840 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry.

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  • TRPS1 is a nuclear protein found in breast epithelial cells and has potential as a breast cancer marker, based on a study analyzing 19,201 samples from various tumor types.
  • In breast carcinomas, low TRPS1 expression correlates with aggressive features like high grade and nodal metastasis, but does not predict patient survival.
  • The combination of TRPS1 and GATA3 immunostaining enhances cancer identification, particularly for breast and salivary gland tumors, while TRPS1 negativity helps differentiate urothelial carcinoma from breast cancer.
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Context.—: Steroidogenic acute regulatory (StAR) protein is a mitochondrial transport protein with a critical regulatory role for steroid hormone production. The tissue distribution of StAR expression is limited to few human normal tissues.

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Cadherin-17 (CDH17) is a membranous cell adhesion protein predominantly expressed in intestinal epithelial cells. CDH17 is therefore considered a possible diagnostic and therapeutic target. This study was to comprehensively determine the expression of CDH17 in cancer and to further assess the diagnostic utility of CDH17 immunohistochemistry (IHC).

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Background: High-mobility group box protein 1 [HMGB1] is a ubiquitous nucleoprotein with immune-regulatory properties following cellular secretion or release in sterile and in infectious inflammation. Stool and serum HMGB1 levels correlate with colitis severity and colorectal cancer [CRC] progression, yet recent reports indicate that HMGB1 mainly operates as an intracellular determinant of enterocyte fate during colitis, and investigations into the roles of HMGB1 in CRC are lacking.

Methods: Using mice with conditional HMGB1-knockout in enterocytes [Hmgb1ΔIEC] and myeloid cells [Hmgb1ΔLysM], respectively, we explored functions of HMGB1 in pathogenetically diverse contexts of colitis and colitis-associated CRC.

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  • GAD2 is a key inhibitory neurotransmitter found mainly in brain and pancreatic islet cells, making it a potential diagnostic marker for tumors.
  • In an analysis of over 19,000 samples from various tumors and normal tissues, GAD2 expression was identified in a small percentage of tumor categories, particularly in neuroendocrine cancers.
  • Combining GAD2 with progesterone receptor (PR) testing enhances diagnostic accuracy for determining pancreatic origins of neuroendocrine neoplasms, achieving high sensitivity and specificity.
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Background: Prostein (P501S), also termed solute carrier family 45 member 3 (SLC45A3) is an androgen regulated protein which is preferentially expressed in prostate epithelial cells. Because of its frequent expression in prostate cancer, prostein was suggested a diagnostic prostate cancer marker.

Methods: In order to comprehensively assess the diagnostic utility of prostein immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

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  • RNA-based multi-gene panels for breast cancer risk assessment can be unreliable due to changes in tumor purity, but multiplex fluorescence immunohistochemistry (mfIHC) offers a better solution.
  • A new automated framework using artificial intelligence for breast cancer detection analyzed 1404 invasive breast cancer cases, achieving a 98.4% accuracy in distinguishing between normal and malignant cells.
  • The study found that a combination of five biomarkers (PR, ER, AR, GATA3, PD-L1) was linked to improved overall survival and provided strong prognostic value, making it an effective independent risk factor for breast cancer prognosis.
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