The aim of this study was to evaluate clinical parameters and expression patterns of Ki-67, cyclin D1 and p53 in odontogenic keratocysts.
In this study, fifty-three patients with 80 odontogenic ...keratocysts were included. The medical records of these patients were reviewed retrospectively. To elucidate the molecular pathogenesis of the disease, the expression of p53, Ki-67 and cyclin D1 was analyzed using immunohistochemistry.
A total of 53 patients (mean age 38 years) with a median follow-up of 4.2 years (ranging from 4 days to 14.4 years) were evaluated. The rates of recurrence and post-operative complications varied depending on the surgical approach: cystectomy and peripheral ostectomy led to manageable low rates of complications and recurrence frequency. Immunohistochemical evaluation revealed that all lesions were positive for Ki-67 and cyclin D1 expression. The expression of Ki-67 was associated with the degree of inflammation. Cyclin D1 was expressed significantly higher in syndrome-associated keratocystic lesions. In contrast to non-syndromal lesions, all syndromal lesions expressed p53.
This investigation demonstrates that the pathogenesis of syndromal keratocysts appears to differ from sporadic odontogenic keratocysts. Additionally, the primary and recurrent non-syndromal keratocysts have a similar etiology, as no differences in the expression patterns of Ki-67, p53 and cyclin D1 were observed.
Abstract Background Increases in incidence of oropharyngeal squamous cell carcinoma (OPSCC) in countries with falling tobacco use have been attributed to a growing role of human papilloma virus (HPV) ...in the carcinogenesis. Trends of HPV prevalence in populations with persistently high portions of smokers are poorly characterised. Patients and methods Registry data from East Germany were used to determine incidence trends between 1998 and 2011. Data from patients treated at the Charité University Medicine Berlin between 2004 and 2013 (cohort 1, N = 436) were used for estimation of trends in HPV prevalence, smoking and survival. HPV prevalence was prospectively confirmed in cohort 2 ( N = 213) comprising all primary HNSCC cases at the Charité in 2013. Results Between 1998 and 2011 incidence of both OPSCC and non-OPSCC increased. An increase in HPV prevalence (% of HPV+ cases in 2004–2006 versus 2012–2013: 27% versus 59%, P = 0.0004) accompanied by a moderate decrease in the portion of current smokers was observed in OPSCC but not in non-OPSCC. The change in disease epidemiology in OPSCC was associated with significant improvement in overall survival. Increased HPV prevalence in OPSCC (48%) compared to non-OPSCC (11%) was confirmed in cohort 2. Conclusions Despite clear differences to the United States in terms of tobacco use, the increase in OPSCC incidence in a European population was also mainly attributed to HPV, and the HPV status significantly affected prognosis. For clinical trial design it is important to consider the large group of smokers within HPV-induced OPSCC.
Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory ...molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 × 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.
Aims : To investigate T‐bet expression profiles in various lymphoid tissue diseases caused by intracellular pathogens and to compare them in disorders without an infective aetiology. Murine and in ...vitro experiments have shown that the expression/induction of T‐bet, the master regulator of Th1 differentiation, can be achieved by obligate intracellular pathogens and high interferon (IFN)‐γ levels.
Methods : Lymph node biopsies were analysed immunohistochemically employing single and double labelling for T‐bet and CD20, CD4, CD8 and CD30 detection.
Results : In disorders associated with high IFN‐γ levels and intracellular pathogens (infectious mononucleosis, HIV‐associated lymphadenopathy, cat‐scratch disease, and toxoplasmic lymphadenitis), T‐bet‐expressing CD4 cells were accompanied by significant numbers of T‐bet‐positive CD8 and B cells. A similar profile was also found in histiocytic necrotizing (Kikuchi) lymphadenitis, a disease of unknown cause. In contrast, T‐bet expression in disorders without an infective aetiology was observed in only a small portion of lymphocytes.
Conclusions : Increased T‐bet expression does not only identify intracellular infections in lymphoid tissue associated with high IFN‐γ levels, but also implies that, under these conditions, it becomes induced in B cells, which apparently support the Th1 response. T‐bet expression in Kikuchi lymphadenitis underscores the hypothesis that it is caused by an intracellular microorganism.
Aims : To clarify the distribution and lineage allocation of T‐bet‐expressing cells in coeliac disease (CD) and in enteropathy‐type T‐cell lymphoma (ETTCL). The detection of elevated levels of ...interferon‐gamma, interleukin‐18 and the key regulator of Th1 helper immune response T‐bet in CD biopsies led to the view that CD is the result of a Th1 response to gluten. It remains unknown whether T‐bet is expressed in cryptic and overt ETTCL.
Methods : Specimens from 20 patients with CD, five patients with cryptic and 10 patients with overt ETTCL were analysed by immunohistology employing single and double labellings for T‐bet and CD4 or CD8 antigens.
Results : In CD specimens nearly all intraepithelial CD8 cells and many CD4 cells in the lamina propria expressed T‐bet. Cryptic ETTCL showed T‐bet expression in the intraepithelial neoplastic cells while T‐bet+ CD4 cells in the lamina propria were rare. Overt ETTCL showed T‐bet expression in cases with non‐anaplastic morphology. In addition, a proportion of bystander T cells expressed T‐bet.
Conclusions : Morphological evidence proves that while T‐bet orchestrates a CD4‐ and CD8‐based Th1 reaction in CD, its expression shifts to the neoplastic intraepithelial compartment of cryptic ETTCL and becomes absent or lost in anaplastic overt ETTCL.
B cell differentiation is controlled by a complex network of lineage-restricted transcription factors. How perturbations to this network alter B cell fate remains poorly understood. Here we show that ...classical Hodgkin lymphoma tumor cells, which originate from mature B cells, have lost the B cell phenotype as a result of aberrant expression of transcriptional regulators. The B cell-specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2. Both factors antagonized the function of the B cell-determining transcription factor E2A. As a result, expression of genes specific to B cells was lost and expression of genes not normally associated with the B lineage was upregulated. These data demonstrate the plasticity of mature human lymphoid cells and offer an explanation for the unique classical Hodgkin lymphoma phenotype.
Introduction/ Background More than six years ago – accompanying the start of the new study program “Modellstudiengang” – we began a virtual microscopy program for our students. This started with ...slides to accompany the course to use during the lesson and for review of the slides at home (or in the library). But we wanted to go further. How far have we come? Aims Our aim was to provide our students with more benefi- cial information and to increase the amount of material available - in the form of slides and accompanying exercises. A secondary goal was streamlining the education of our students (fewer slides to manage and better opportuni- ties for students to prepare for lessons). Methods The slides were scanned using NanoZoomer 2.0-HT slide scanner. The virtual slides were made available to students using Slidebox system (version 4.4.3.) in three different ways:We provided annotated slides with healthy (physio- logical) and diseased (pathological) samples to ac- company the entire course. Some of the slides were for use during lessons, others as supplementary material. • The virtual slides were integrated into a new style of lecture (“blended learning”) mixing learning opportu- nities from case reports, including clinical information; radiological images; and virtual slides. To review acquired knowledge memory-quizzes were used. • We complement the cases seen in the practical course “Autopsy – How, why, to what end?” with histology. Thus students are able to have a complete overview of the case from clinical history, to macroscopic findings and their correlation with the microscopic findings, to the final report. Results Usually the students were suprised, when they first come in contact with the virtual microscopy. But the Initial suprise yields to experimentation and getting used to it. Virtual microscopy is not only just a part, but an import- ant part of our education.
Zusammenfassung
Seit Jahrzehnten sind unspezifische Wirkungen, die starke Toxizität und die sich (oft) entwickelnde Resistenz gegen Krebsmedikamente das Hauptproblem der Onkologie. Die klinische ...Pathologie spielt für die Auswahl der neuen, gezielt antineoplastisch wirkenden Substanzen eine zunehmende Rolle. Die Einführung und translationale Adaptation zahlreicher Methoden der Immunologie und Molekularbiologie an die Besonderheiten der gewebebasierten Diagnostik führte dazu, dass in pathologischen Routineuntersuchungen das Tumorgewebe vermehrt einer systematischen Immunphäno- und molekularen Genotypisierung unterzogen wird. Dieser multimodale Ansatz ist heute Standard für zahlreiche Tumorentitäten und wird in den nächsten Jahren weiter ausgeweitet werden. Hieraus resultiert die faszinierende Möglichkeit, zusätzlich zum vorhandenen Diagnosespektrum der klinischen Pathologie verstärkt prädiktive Biomarker zu bestimmen, um dem klinischen Onkologen therapeutisch relevante Daten zur Verfügung stellen zu können.
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