Pathobiology of classical Hodgkin lymphoma.

The World Health Organization has acknowledged the malignant nature of classical Hodgkin lymphoma (cHL), which encompasses four histological subtypes. The diagnosis of cHL is based on the detection of malignant Hodgkin and Reed-Sternberg cells (HRSC) confirmed by immunophenotyping and the detection of growth patterns specific to each histological subtype. The pathologic HRSC arise from germinal center or immediate postgerminal cells that lack detectable immunoglobulin/B-cell antigen receptor expression, with a consequent loss of B-cell identity; very few cHL cases are of T-cell origin.

Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a significant number of cells reside in early G1-phase.

Background And Aims: Chronic lymphocytic leukaemia (CLL) is a frequent non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Assessment of cell cycle phase kinetics might be important for prediction of clinical behaviour and prognosis.

Methods: Distribution of neoplastic cells in CLL within the cell cycle was evaluated by determining the labelling indices (LI, i.

Life with a single isoform of Akt: mice lacking Akt2 and Akt3 are viable but display impaired glucose homeostasis and growth deficiencies.

To address the issues of isoform redundancy and isoform specificity of the Akt family of protein kinases in vivo, we generated mice deficient in both Akt2 and Akt3. In these mice, only the Akt1 isoform remains to perform essential Akt functions, such as glucose homeostasis, proliferation, differentiation, and early development. Surprisingly, we found that Akt2(-/-) Akt3(-/-) and even Akt1(+/-) Akt2(-/-) Akt3(-/-) mice developed normally and survived with minimal dysfunctions, despite a dramatic reduction of total Akt levels in all tissues.

T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17.

Experimental autoimmune myocarditis (EAM) appears after infectious heart disease, the most common cause of dilated cardiomyopathy in humans. Here we report that mice lacking T-bet, a T-box transcription factor required for T helper (Th)1 cell differentiation and interferon (IFN)-gamma production, develop severe autoimmune heart disease compared to T-bet+/+ control mice. Experiments in T-bet-/- IL-4-/- and T-bet-/- IL-4Ralpha-/- mice, as well as transfer of heart-specific Th1 and Th2 cell lines, showed that autoimmune heart disease develops independently of Th1 or Th2 polarization.

Angiogenesis in nodal B cell lymphomas: a high throughput study.

Aim: To assess the biological significance of vascular endothelial growth factor (VEGF) A, VEGF receptor (Flk-1) and cyclooxygenase 2 (COX2) expression with respect to microvessel density (MVD), proliferative activity (Ki-67), expression of p53 and clinical presentation in a large cohort of nodal B cell lymphomas.

Methods: An immunohistochemical and morphometric study was performed on a validated tissue microarray containing 271 B cell lymphoma specimens, 197 of which included follow-up data. Statistical assessment was done by Pearson's chi(2) test, Spearman's rank correlation coefficient, analysis of variance and survival analysis.

Thermal preconditioning protects the human internal mammary artery from hypoxia/re-oxygenation-induced damage.

1. Preconditioning has been demonstrated to ameliorate ischaemia/reperfusion injury in several cells and tissues. Therefore, in the present study we investigated whether preconditioning of human bypass grafts, internal mammary artery (IMA) and saphenous vein (SV) induces heat shock protein (Hsp) expression and reduces apoptosis in response to subsequent hypoxia/re-oxygenation damage in both vessels.

Plasma cell quantification in bone marrow by computer-assisted image analysis.

Background: Minor and major criteria for the diagnosis of multiple meloma according to the definition of the WHO classification include different categories of the bone marrow plasma cell count: a shift from the 10-30% group to the > 30% group equals a shift from a minor to a major criterium, while the < 10% group does not contribute to the diagnosis. Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of this study was (i) to establish a digital image analysis system able to quantify bone marrow plasma cells and (ii) to evaluate two quantification techniques in bone marrow trephines i.

Construction and validation of a bone marrow tissue microarray.

Background: The use of tissue microarrays (TMAs) is now a generally accepted method for the investigation of solid tumours. However, little is known about the applicability of the TMA technique for analysis of patients with acute leukaemia. A bone marrow (BM)-TMA analysis with 15 different immunohistochemical markers was performed.

[The diagnostic and predictive role of kit (CD117)].

KIT (CD117) is a 145-KD transmembrane glycoprotein that is the product of the kit-gene. As a member of the subclass III family of receptor tyrosine kinases, KIT is closely related to the receptors for platelet derived growth factor alpha and beta (PDGF-A and B), macrophage colony stimulating factor (M-CSF), and FLT3 ligand. The ligand for KIT, stem cell factor (SCF), also known as steel factor or mast cell growth factor promotes the dimerisation and autophosphorylation of KIT receptors.

Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer.

Objective: Currently available clinical and molecular factors provide still an insufficient prognostic and predictive assessment for patients with epithelial ovarian cancer (EOC). To identify a potential molecular target and prognostic/predictive factor for EOC, we investigated in a retrospective study the prognostic value of Ep-CAM overexpression in EOC.

Methods: We assessed by immunohistochemistry the expression of the Ep-CAM antigen on tissue microarrays containing paraffin-embedded tissue samples of 199 patients with documented EOC.

Diffuse large B-cell lymphoma with overexpression of cyclin e substantiates poor standard treatment response and inferior outcome.

Purpose: Gold standard to predict survival and stratify patients for risk-adapted therapy in diffuse large B-cell lymphoma (DLBCL) is the international prognostic index, although it does not consider the molecular heterogeneity of DLBCL. Deregulation of cyclin E (CCNE) is a strong predictor of poor prognosis in some neoplastic diseases. In tumor cells, it induces chromosomal instability with an increased rate of aneuploidy/polyploidy.

High rate of molecular alteration in histologically tumour-free bronchial epithelium of NSCLC patients detected by multicolour fluorescence in situ hybridisation.

Detection of molecular abnormalities could provide an essential tool for the diagnosis of non-small cell lung cancer (NSCLC) and defining patients at risk for early relapse. Fluorescence in situ hybridisation (FISH) targeting 17 gene loci was applied to determine the frequency of molecular alteration in NSCLC probes and adjacent tumour-free bronchial epithelium. FISH was performed on fresh frozen specimens from 76 patients with histologically confirmed NSCLC and 54 specimens of adjacent tumour-free tissue.

Precursor B lymphoblastic leukemia 32 months after local therapy for a primary extramedullary myeloid cell tumor.

A primary extramedullary myeloid cell tumor (pEMT) of an inguinal lymph node was completely excised without subsequent anti-tumor therapy in a 6-year-old child. Clinical observation and monitoring of blood and bone marrow (BM) did not reveal any pathologic results before 32 months, when a precursor B lymphoblastic leukemia was diagnosed. Identical T-cell receptor gamma rearrangement in nodal pEMT and in precursor B lymphoblastic leukemia in BM indicates a clonal relationship of these two tumors.

High predictive value of epidermal growth factor receptor phosphorylation but not of EGFRvIII mutation in resected stage I non-small cell lung cancer (NSCLC).

Aims: Overexpression and mutation of epidermal growth factor regulator (EGFR) are frequently found in the carcinogenesis of non-small cell lung cancer (NSCLC). Because targeting of this receptor has proven therapeutic efficacy, studying EGFR has become a matter of particular scientific interest. The present study analysed the EGFR receptor, rate of EGFRvIII mutations, and rate of activated phosphorylated EGFR (pEGFR) by immunohistochemistry on cryostat sections.

MyD88 signaling controls autoimmune myocarditis induction.

Background: Experimental autoimmune myocarditis (EAM) is a CD4+ T-cell-mediated mouse model of postviral cardiomyopathy. Activation of interleukin-1 type 1 and Toll-like receptors that share the common downstream adaptor molecule MyD88 is required for disease induction. The specific role of MyD88 in myocarditis, however, is not known.

Age and hemoglobin level emerge as most important clinical prognostic parameters in patients with osteomyelofibrosis: introduction of a simplified prognostic score.

The course of disease in patients with myelofibrosis is highly variable, with survival ranging from few months to many years. Several prognostic models have been established, with the LILLE score now most commonly used. However, in recent series, the latter scoring system repeatedly failed to discriminate patients with intermediate and poor prognosis.

Cancer-associated carbohydrate identification in Hodgkin's lymphoma by carbohydrate array profiling.

Tumor-associated carbohydrates have potential not only as diagnostic tools but also as specific therapeutic targets. Their identification, however, has been hampered by the lack of suitable technologies. We used carbohydrate array technology to compare serum antibody (IgG and IgM) levels against 37 different carbohydrates between classical Hodgkin's lymphoma (cHL) patients and age/sex-matched healthy controls.

Epidemiology of non-Hodgkin lymphomas in Tyrol/Austria from 1991 to 2000.

Aims: To analyse the entity specific incidence and disease specific survival (DSS) of non-Hodgkin lymphomas (NHLs) in Tyrol/Austria, 1991-2000.

Methods: Data from 1307 NHLs (excluding primary cutaneous lymphomas and monoclonal gammopathies of undetermined significance) were obtained. Current status was available for all patients.

Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis.

Background: Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and have been found to be relevant markers for prognosis in a variety of tumours. The aim of this study was to assess the proliferative activity of diffuse large B-cell lymphoma (DLBCL) in tissue microarray (TMA) using one of the minichromosome maintenance proteins (Mcm2) and to explore its potential value to predict prognosis.

Methods: Immunohistochemistry for Mcm2 was performed on TMAs constructed from 302 cases of DLBCL.

Marginal zone lymphoma of the lacrimal gland spreading to the lung and the bone marrow 11 years after first symptoms.

We report on the case of a 52-year-old male presenting with an extranodal marginal zone lymphoma of the mucosa-associated tissue (MALT lymphoma) in the lung 11 years after radiotherapy for a MALT lymphoma of the lacrimal gland, which was primarily diagnosed as dacryoadenitis. Both tumors were investigated by immunohistochemistry and molecular techniques demonstrating their clonal genetic relationship. Both harbored the t(14;18)(q32;q21) and a trisomy 3 and showed identical immunoglobulin heavy-chain gene rearrangements.

Cyclin B1 expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin's lymphoma in the Western world; it is characterized by marked genetic, morphological and clinical heterogeneity. The identification of prognostic markers could help to develop risk-adapted treatment strategies. As proliferation of cells is essential for tumour growth, analysis of the cell cycle and its individual phases might give additional information on tumour progression and clinical behaviour.

Tissue microarray technology: principles, pitfalls and perspectives--lessons learned from hematological malignancies.

Detection, validation and incorporation into clinical use of new diagnostic, prognostic and therapeutic molecular targets in modern medical science should be time- and cost-efficient. Here, we discuss the principles, advantages, disadvantages and possible pitfalls of tissue microarray (TMA) technology, a powerful tool for high throughput large-scale morphological in situ analysis of molecular targets. Based on recent observations from molecular profiling of hematological malignancies, we review potential TMA applications assessing molecular targets in large collectives of tissue specimens.

Rare expression of T-cell markers in classical Hodgkin's lymphoma.

Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphoma are primarily of B-cell origin, although there are instances of T-cell antigen expression suggesting T-cell origin. We comprehensively analyzed expression of various T-cell antigens in 259 classical Hodgkin's lymphoma cases using the tissue microarray technique. Expression of the T-cell antigens CD2, CD3, CD4, CD5, CD7 and CD8 was assessed by immunohistochemistry.