Rana Ahmed El Ghondakly, Salwa Ibrahim El Haddad, Magda Mohamed AbdelSalam, Ola Hassan Nada, Rola Mohamed Farid, Laila M. Farid
{"title":"Immunohistochemical expression of SATB2 and PAX8 in differentiating primary from metastatic ovarian mucinous neoplasms","authors":"Rana Ahmed El Ghondakly, Salwa Ibrahim El Haddad, Magda Mohamed AbdelSalam, Ola Hassan Nada, Rola Mohamed Farid, Laila M. Farid","doi":"10.1111/apm.13449","DOIUrl":"10.1111/apm.13449","url":null,"abstract":"<p>Accurate stratification of an ovarian mucinous neoplasm as primary or secondary is always challenging as they show overlapping histomorphological and immunohistochemical features. Immunohistochemical staining for SATB2 and PAX8 was performed on 80 cases of mucinous ovarian neoplasms subdivided into 53 primary [25 primary ovarian mucinous carcinomas (POMCs) and 28 mucinous borderline tumors (MBTs)] and 27 secondary (12 of colonic origin, 7 of appendiceal origin, and 8 of gastric origin). Expression was correlated with different clinicopathologic parameters. PAX8-positive immunostaining was detected in 38 out of 53 cases (71.69%) of primary ovarian mucinous neoplasms (POMNs) with null positivity in the secondary ovarian mucinous tumors (0/27). SATB2-positive expression was detected in 16 out of 27 cases (59.26%) of the secondary ovarian mucinous tumors. None of the studied POMNs showed any positive immunostaining for SATB2 (0/53). A profile of SATB2<sup>−</sup>/PAX8<sup>+</sup> and SATB2<sup>+</sup>/PAX8<sup>−</sup> can be used to differentiate POMNCs from secondary ovarian mucinous tumors of GI origin, respectively, with 100% specificity. PAX8 expression is associated with some clinicopathologic parameters providing the basis for the possible usage of PAX8 as prognostic marker.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 10","pages":"706-717"},"PeriodicalIF":2.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emilie C. Pedersen, Christian Johann Lerche, Franziska Angelica Schwartz, Oana Ciofu, Joana Azeredo, Kim Thomsen, Claus Moser
{"title":"Bacteriophage therapy and infective endocarditis – is it realistic?","authors":"Emilie C. Pedersen, Christian Johann Lerche, Franziska Angelica Schwartz, Oana Ciofu, Joana Azeredo, Kim Thomsen, Claus Moser","doi":"10.1111/apm.13455","DOIUrl":"10.1111/apm.13455","url":null,"abstract":"<p>Infective endocarditis (IE) is a severe infection of the inner heart. Even with current standard treatment, the mean in-hospital mortality is as high as 15–20%, and 1-year mortality is up to 40% for left-sided IE. Importantly, IE mortality rates have not changed substantially over the past 30 years, and the incidence of IE is rising. The treatment is challenging due to the bacterial biofilm mode of growth inside the heart valve vegetations, resulting in antibiotic tolerance. Achieving sufficient antibiotic anti-biofilm concentrations in the biofilms of the heart valve vegetations is problematic, even with high-dose and long-term antibiotic therapy. The increasing prevalence of IE caused by antibiotic-resistant bacteria adds to the challenge. Therefore, adjunctive antibiotic-potentiating drug candidates and strategies are increasingly being investigated. Bacteriophage therapy is a reemerging antibacterial treatment strategy for difficult-to-treat infections, mainly biofilm-associated and caused by multidrug-resistant bacteria. However, significant knowledge gaps regarding the safety and efficacy of phage therapy impede more widespread implementation in clinical practice. Hopefully, future preclinical and clinical testing will reveal whether it is a viable treatment. The objective of the present review is to assess whether bacteriophage therapy is a realistic treatment for IE.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 10","pages":"675-687"},"PeriodicalIF":2.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the cross-protection of the Vero cell-derived attenuated influenza vaccines with compound adjuvant, through intranasal immunization","authors":"Liu Ze, Song Shaohui, Huang Jinhai, Gao Hui","doi":"10.1111/apm.13448","DOIUrl":"10.1111/apm.13448","url":null,"abstract":"<p>This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 10<sup>5</sup> PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 μg/mL of carbopol971P and 50 μg/mL of tetanus toxin. That vaccination was called <i>catt</i>-<i>flu</i>. And it employed the GYZZ02 vaccine (commercialized freeze-dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That <i>catt</i>-<i>flu</i> program could induce more cross-protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non-inferiority titter compared with the chicken embryo-derived GYZZ02 vaccine on safe and effect. The Vero cell-derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as <i>catt</i>-<i>flu</i> program.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 10","pages":"741-753"},"PeriodicalIF":2.2,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jannik Fonager, Nikolaj Julian Skrøder Nytofte, Christian Højte Schouw, Christian B. Poulsen, Lothar Wiese, Anders Fomsgaard, Marc Bennedbæk, Morten Rasmussen, Xiaohui Chen Nielsen
{"title":"Emergence and fixation of SARS-CoV-2 minority variants in a chronically infected patient receiving therapy in Denmark","authors":"Jannik Fonager, Nikolaj Julian Skrøder Nytofte, Christian Højte Schouw, Christian B. Poulsen, Lothar Wiese, Anders Fomsgaard, Marc Bennedbæk, Morten Rasmussen, Xiaohui Chen Nielsen","doi":"10.1111/apm.13454","DOIUrl":"10.1111/apm.13454","url":null,"abstract":"<p>SARS-CoV-2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long-term SARS-CoV-2 infection with the pre-VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi-species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS-CoV-2 among immunocpromised patients.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 10","pages":"734-740"},"PeriodicalIF":2.2,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marit Bernhardt, Leonie Weinhold, Christine Sanders, Oliver Hommerding, Jan-Frederic Lau, Marieta Toma, Verena Tischler, Matthias Schmid, Tomasz Zienkiewicz, Ralf Hildenbrand, Peter Gerlach, Hui Zhou, Martin Braun, Gunnar Müller, Erich Sieber, Christian Marko, Glen Kristiansen
{"title":"Peer-to-peer validation of Ki-67 scoring in a pathology quality circle as a tool to assess interobserver variability: are we better than we thought?","authors":"Marit Bernhardt, Leonie Weinhold, Christine Sanders, Oliver Hommerding, Jan-Frederic Lau, Marieta Toma, Verena Tischler, Matthias Schmid, Tomasz Zienkiewicz, Ralf Hildenbrand, Peter Gerlach, Hui Zhou, Martin Braun, Gunnar Müller, Erich Sieber, Christian Marko, Glen Kristiansen","doi":"10.1111/apm.13451","DOIUrl":"10.1111/apm.13451","url":null,"abstract":"<p>Ki-67, a nuclear protein expressed in all stages of cellular proliferation, is a valuable tool to assess tumor proliferation and has been linked to more aggressive tumor behavior. However, interlaboratory staining heterogeneity and inter-observer variability challenge its reproducibility. Round Robin tests are a suitable tool to standardize and harmonize immunohistochemical and molecular analyses in histopathology. The study investigates the interrater and interlaboratory reproducibility of Ki-67-scoring using both manual and automated approaches. Unstained TMA slides comprising diverse tumor types (breast cancer, neuroendocrine tumors, lymphomas, and head and neck squamous cell carcinoma) were distributed to six pathology laboratories, each employing their routine staining protocols. Manual and automated scoring methods were applied, and interrater and interlaboratory agreement assessed using intraclass correlation coefficients (ICC). The results highlight good-to-excellent reliability overall, with automated scoring demonstrating higher consistency (ICC 0.955) than manual scoring (ICC 0.871). Results were more variable when looking at the individual entities. Reliability remained good for lymphomas (ICC 0.878) and breast cancer (ICC 0.784) and was poor in well-differentiated neuroendocrine tumors (ICC 0.354). This study clearly advocates standardized practices and training to ensure consistency in Ki-67-assessment, and it demonstrates that this can be achieved in a peer-to-peer approach in local quality-circles.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 10","pages":"718-727"},"PeriodicalIF":2.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Celebrating a century of APMIS: a legacy of pathology, microbiology, and immunology","authors":"Bodil Norrild, Ulrik Ralfkiaer","doi":"10.1111/apm.13452","DOIUrl":"10.1111/apm.13452","url":null,"abstract":"<p>This manuscript commemorates the 100th anniversary of APMIS, highlighting its evolution from a regional journal, founded in 1924 as Acta Pathologica et Microbiologica Scandinavica, to an international platform fostering global collaboration in pathology, microbiology, and immunology. The journal's inception was driven by Ulrik Quensel's vision in 1919, leading to the establishment of the Northern Pathological Society and the launch of the journal in 1924. APMIS has consistently published landmark research, including significant contributions from prominent. These studies have advanced understanding in fields such as pathology, microbiology, and immunology. The journal expanded its scope in the 1970s to include immunology, rebranding as APMIS in the mid-1980s. Recent decades have seen a continued commitment to cutting-edge research and an increasing impact factor. As APMIS transitions to an Open Access model under Wiley, it will be renamed the PMI Journal (Pathology, Microbiology, and Immunology) to reflect its global reach and dedication to scientific excellence. This centennial celebration acknowledges the contributions of editors, authors, and readers, looking forward to future advancements in biomedical research.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling the intricacies of cancer-associated fibroblasts: a comprehensive review on metabolic reprogramming and tumor microenvironment crosstalk","authors":"Sana Ahuja, Niti Sureka, Sufian Zaheer","doi":"10.1111/apm.13447","DOIUrl":"10.1111/apm.13447","url":null,"abstract":"<p>Cancer-associated fibroblasts (CAFs) are crucial component of tumor microenvironment (TME) which undergo significant phenotypic changes and metabolic reprogramming, profoundly impacting tumor growth. This review delves into CAF plasticity, diverse origins, and the molecular mechanisms driving their continuous activation. Emphasis is placed on the intricate bidirectional crosstalk between CAFs and tumor cells, promoting cancer cell survival, proliferation, invasion, and immune evasion. Metabolic reprogramming, a cancer hallmark, extends beyond cancer cells to CAFs, contributing to the complex metabolic interplay within the TME. The ‘reverse Warburg effect’ in CAFs mirrors the Warburg effect, involving the export of high-energy substrates to fuel cancer cells, supporting their rapid proliferation. Molecular regulations by key players like p53, Myc, and K-RAS orchestrate this metabolic adaptation. Understanding the metabolic symbiosis between CAFs and tumor cells opens avenues for targeted therapeutic strategies to disrupt this dynamic crosstalk. Unraveling CAF-mediated metabolic reprogramming provides valuable insights for developing novel anticancer therapies. This comprehensive review consolidates current knowledge, shedding light on CAFs' multifaceted roles in the TME and offering potential targets for future therapies.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"906-927"},"PeriodicalIF":2.2,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamics of endemic human coronavirus and SARS-CoV-2 in a hospital of Madrid, Spain. Retrospective study from June 2020 to July 2023","authors":"Rojo-Marcos Gerardo, Hernández-García Guiomar, González-Sarria Ander, Guerrero-Cañar Carlos Andrés, Arévalo-Cañas Coral","doi":"10.1111/apm.13446","DOIUrl":"10.1111/apm.13446","url":null,"abstract":"<p>An observational and retrospective study was carried out to analyse HCoV positivity from a multiplex PCR respiratory panel and RT-PCR for SARS-CoV-2 in respiratory samples from 1 June 2020 to 31 July 2023 at the Príncipe de Asturias University Hospital (HUPA) in Alcalá de Henares, Madrid, Spain. Out of 2802 respiratory panels, 1258 (44.8%) turned out positive. HCoV was detected in 114 (4%) cases (range 0–23; median 1.5; IQR 0–3.75) with positivity rates ranging from 0% to 14%. All four variants of HCoV circulated, and OC-43 was the most common in 62.3% of cases. After the onset of the pandemic, the HCoV season was delayed 22 weeks, with a peak positivity of 9% in the summer of 2021, showing an inverse relationship with the alpha and delta waves of SARS-CoV-2. In the two subsequent autumn–winter seasons, HCoV positivity increased (11–14%) with a reduction in the summer of 2022 and 2023 following the emergence of the omicron variant and the relaxation of social distancing measures. The seasonal spread pattern of endemic HCoV might be returning to normal in our region and likely in other temperate zones of the northern hemisphere after 3 years of the pandemic.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 9","pages":"657-662"},"PeriodicalIF":2.2,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Ley Ringgaard, Torben Steiniche, Søren Palmelund Krag
{"title":"Routine use of MSI testing in colorectal cancer using a proposed algorithm","authors":"Marie Ley Ringgaard, Torben Steiniche, Søren Palmelund Krag","doi":"10.1111/apm.13442","DOIUrl":"10.1111/apm.13442","url":null,"abstract":"<p>Fifteen percent of all colorectal cancers have detectable defects in the mismatch repair system (dMMR). MMR status is used to identify possible Lynch Syndrome (LS) and to determine prognosis and choice of treatment. Two standard techniques for determining MMR status are immunohistochemistry (IHC) and analysis for microsatellite instability (MSI) by PCR. Recently, our department introduced Idylla™ MSI assay as an alternative option to IHC, and as part of this, we introduced a decision algorithm. The purpose of this study was to review the use of the new method and our algorithm and to assess possible false-positive results. Retrospectively, we identified 629 cases of colorectal cancer in which either IHC (336 cases) or Idylla™ MSI (293 cases) was performed. Similar results were obtained by the two methods. IHC detected dMMR in 55 cases (16%) and Idylla™ MSI in 52 cases (18%). In all 52 cases of MSI, subsequent IHC was performed. One case was not confirmed by IHC, but was confirmed by another PCR-based method. Overall, we found that the Idylla™ MSI works well as a screening method for dMMR with no false-positive cases detected. The proposed algorithm was useful and easily applicable.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 9","pages":"632-637"},"PeriodicalIF":2.2,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehmet Ali Karaselek, Tugce Duran, Serkan Kuccukturk, Hulya Vatansev, Pembe Oltulu
{"title":"Changes in T-cell subsets occur in interstitial lung disease and may contribute to pathology via complicated immune cascade","authors":"Mehmet Ali Karaselek, Tugce Duran, Serkan Kuccukturk, Hulya Vatansev, Pembe Oltulu","doi":"10.1111/apm.13445","DOIUrl":"10.1111/apm.13445","url":null,"abstract":"<p>The study aimed to investigate the expression profiles of transcription factors, cytokines, and co-stimulatory molecules in helper T (Th)-cell subsets within bronchoalveolar lavage (BAL) samples of patients with interstitial lung diseases (ILDs). Twenty ILDs patients were included in the study, comprising those with idiopathic pulmonary fibrosis (IPF) (n:8), autoimmune-related ILDs (auto-ILD) (n:4), and orphan diseases (O-ILD) (n:8), alongside five control subjects. Flow cytometry was employed to evaluate the Th to cytotoxic T cell (CTL) ratio in BAL fluid, while cytopathological examination assessed macrophages, lymphocytes, and neutrophils. Quantitative real-time polymerase chain reaction was utilized to investigate the expressions in Th1, Th2, Th17, and regulatory T (Treg) cells. Results revealed elevated Th cell to CTL ratios across all patient groups compared to controls. Furthermore, upregulation of Th1, Th2, Th17, and T-cell factors was observed in all patient groups compared to controls. Interestingly, upregulation of <i>CD28</i> and downregulation of <i>CTLA-4</i> and <i>PD-1</i> gene expression were consistent across all ILDs groups, highlighting potential immune dysregulation. This study provides a comprehensive exploration of molecular immunological mechanisms in ILDs patients, underscoring the dominance of Th2 and Th17 responses and revealing novel findings regarding the dysregulation of <i>CD28</i>, <i>CTLA-4</i>, and <i>PD-1</i> expressions in ILDs for the first time.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 9","pages":"663-671"},"PeriodicalIF":2.2,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}