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E Haralambieva

Publications and source records attributed to E Haralambieva.

9 recordsLinked to original sources

[Extranodal marginal zone B-cell lymphoma of MALT-type].

Extranodal marginal zone B-cell lymphomas of the MALT type constitute, with around 8% of all B-cell lymphomas, the third most frequent lymphoma in the Western hemisphere. Their unifying characteristic principle is their origin in organs that are typically devoid of a regular lymphatic parenchyma ("primary" MALT). In contrast, "secondary" MALT is acquired in these sites by chronic inflammatory processes triggered by chronic infections or autoimmune diseases. The organotypic characteristics of these particular lymphoid tumours are also mirrored by organ-specific precursor lesions and in tumour biology. Usually, MALT-type lymphomas remain confined to their site of origin for a long time, disseminating only late during the course of the disease. Hence, they may be controlled by local treatment (excision, irradiation). Moreover, the distinctive genetic constitution of MALT-type lymphomas, although varying from organ to organ, indicates particular transformation pathways obviously related to the specific precursor lesion and, hence, of organ-specific quality.

Autoimmune Diseases↗

Characterization of chromosomal aberrations in diffuse large B-cell lymphoma (DLBL) by G-banding and spectral karyotyping (SKY).

Cytogenetic chromosome analysis by classical G-banding was supplemented by spectral karyotyping (SKY) in 12 cases of diffuse large B-cell lymphoma (DLBL). SKY is a fluorescence in-situ-based, genome-wide screening technique allowing identification of genetic material even in highly condensed metaphase chromosomes of poor morphology. By simultaneous hybridization of whole chromosome painting probes onto tumor chromosome spreads genetic rearrangements are visualized permitting the clarification of even complex karyotype alterations and the identification of genetic material of previously unknown origin, so-called marker chromosomes. Taking the SKY results into account, we reevaluated the G-banding karyotypes initially carried out, thus generating a more precise karyotype in ten of twelve (83%) cases investigated. In particular, thirteen chromosomal rearrangements not correctly recognized by classical cytogenetics were identified, the genetic origin of seven marker chromosomes was elucidated and three structural genetic rearrangements were redefined. We found SKY to be a valuable technique to establish a definite karyotype in addition to classical cytogenetics.

Chromosome Aberrations↗

Simultaneous detection of the immunophenotypic markers and genetic aberrations on routinely processed paraffin sections of lymphoma samples by means of the FICTION technique.

Disciplines such as morphology, immunophenotyping and genetics widely contributed over decades to the understanding of the cellular mechanisms of cancer. To obtain a greater insight into the complex processes of tumorigenesis, scientists have joined their efforts to combine many of the available techniques. Here, we report on the development of a FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a tool for the Investigation of Neoplasms) technique that allows a simultaneous detection of immunophenotypic markers and genetic aberrations on routinely processed lymphoma samples. As the antigen retrieval method seems to play an important role in the final results, we tested the pressure-cooking method at different times (2, 4 and 8 min) using three different buffers (EDTA, Tris-EDTA and citrate), resulting in improved sensitivity for the detection of both immunophenotypic markers and genetic aberrations. We also applied this method to different types of lymphoma using double immunofluorescence assays (including CD30, CD20, CD8 monoclonal antibodies) and several fluorescence in situ hybridization probes to demonstrate that the FICTION technique could be easily applied on paraffin sections in different combinations for the diagnosis and research of cancer.

Buffers↗

Tyrosine phosphorylation in human lymphomas.

In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated whether oncogenic tyrosine kinase activation also occurs in other categories of lymphoma by staining 145 cases of lymphoma covering those tumours with a range of different subtypes including those with morphological similarity to ALK-positive anaplastic large cell lymphoma (ALCL). Twelve cases of the borderline malignant disorder lymphomatoid papulosis were also studied. Twenty seven of the 28 cases of ALK-positive ALCL showed the extensive cytoplasmic labelling for phosphotyrosine in the neoplastic cells. The remaining case containing moesin-ALK exhibited membrane-associated phosphotyrosine expression. There was no nuclear phosphotyrosine labelling in any of the ALK-positive ALCL, even though ALK was present within the cell nuclei in 23 of the tumours. Variable degrees of phosphotyrosine labelling, usually membrane-restricted, were observed in 7/40 cases of ALK-negative ALCL, 9/29 cases of diffuse large B-cell lymphoma, 3/6 cases of mediastinal B-cell lymphoma, 2/7 cases of Hodgkin's lymphoma, 3/6 cases of peripheral T-cell lymphomas unspecified, 4/6 cases of B-cell chronic lymphocytic leukaemia, 2/6 cases of follicular lymphomas and 2/12 cases of lymphomatoid papulosis studied. However none of these phosphotyrosine-positive cases showed the strong cytoplasmic labelling comparable to that seen in ALK-positive lymphoma. We conclude that activation of a tyrosine kinase is probably not a major oncogenic event in lymphomas other than ALK-positive ALCL.

Cell Nucleus↗

Anaplastic large-cell lymphomas of B-cell phenotype are anaplastic lymphoma kinase (ALK) negative and belong to the spectrum of diffuse large B-cell lymphomas.

There is controversy in the literature as to whether anaplastic large-cell lymphoma of B-cell phenotype is related to the t(2;5)-positive T- or 'null' cell lymphoma of the same morphology. We report a study of 24 lymphomas with morphological features of anaplastic large-cell lymphoma which expressed one or more B-cell markers and lacked T-lineage markers. Clinical features were more in keeping with large B-cell lymphoma than with classical t(2;5)-positive anaplastic large-cell lymphoma, and immunostaining for anaplastic lymphoma kinase (ALK) protein provided no evidence for the (2;5) translocation (or one of its variants). The staining patterns for CD20 and CD79 were typical of diffuse large B-cell lymphoma, CD30 expression was variable, and most cases (15/22) lacked epithelial membrane antigen (EMA). These findings support the view that 'B-cell anaplastic large-cell lymphoma' is unrelated to t(2;5)-positive (ALK-positive) lymphoma, and that it represents a morphological pattern occasionally encountered among diffuse large B-cell lymphomas. By the same reasoning, most tumours diagnosed as 'ALK-negative anaplastic large-cell lymphoma of T-cell or null phenotype' probably belong to the spectrum of peripheral T-cell lymphomas.

Adolescent↗

Lymphocyte-specific protein 1: a specific marker of human leucocytes.

While both murine and human homologues of the LSP1 gene (lymphocyte-specific gene 1) and its protein products have been identified, studies on human LSP1 have been limited. The present report describes a detailed immunocytochemical study of the distribution and localization of human LSP1 in both normal and neoplastic cells and tissues. The specificity of the monoclonal anti-LSP1 reagent was confirmed by expression cloning and transfection studies. The intracellular 60 000 MW LSP1 protein was found to be present in peripheral blood B cells, monocytes and granulocytes but absent in a subpopulation of circulating T cells (10-15% of CD3-positive T cells). The presence of LSP1 protein in medullary thymocytes, but only in scattered cortical thymocytes, provided additional evidence for heterogeneity of expression in T cells. Novel observations also included the presence of LSP1 in plasma cells, dendritic cells and Langerhans' cells. The leucocyte-restricted distribution of LSP1 protein means that it may play an important role in haematopathology. LSP1 protein was detected in a wide range of leukaemias and lymphomas, particularly of B-cell origin, and in tumour cells in classical Hodgkin's disease. Of interest was the indication of a reciprocal relationship in the expression of LSP1 and ALK (anaplastic lymphoma kinase) proteins in patients with anaplastic large cell lymphoma. As the anti-LSP1 reagent used in the present study recognizes a formalin-resistant epitope it should be of considerable value in the diagnosis of routinely fixed material.

Anaplastic Lymphoma Kinase↗

ALK-positive lymphoma: a single disease with a broad spectrum of morphology.

The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the expression of a chimeric NPM-ALK protein that can be detected by the ALK1 monoclonal antibody. This report describes the morphologic and phenotypic spectrum of 123 cases of lymphoma that all express ALK protein. The results provide strong evidence that the morphologic patterns of ALCL described in previous reports as representing possible subtypes of ALCL, eg, common type, lymphohistiocytic, or small cell patterns, are morphologic variants of the same disease entity. All of these morphologic patterns could be found within this series, and in some patients different subtypes coexisted in a single biopsy or were found in successive biopsies from a single patient. The link between these morphologic subtypes is further reinforced by the presence in all cases of a highly characteristic large cell, with an eccentric nucleus and an eosinophilic paranuclear region. We suggest that this cell can be considered as a major distinguishing feature of ALK-positive lymphomas. Another characteristic of these tumors was the perivascular pattern of neoplastic cell infiltration seen in a significant number of cases. In addition to ALK protein, all tumors expressed epithelial membrane antigen and lacked CD15, features that may be of value in differentiating ALCL from Hodgkin's disease. In the majority of cases (84%), malignant cells showed both a cytoplasmic and nuclear staining for ALK1 and thus presumably carried the 2;5 translocation, but staining was restricted to the cytoplasm in a few cases, suggesting that translocations other than t(2;5) may induce expression of ALK protein. We conclude from this study that ALK-positive neoplasms represent a distinct entity. Because their morphology is often neither anaplastic nor large cell, we suggest that they should henceforward be referred to as ALK lymphomas.

Adolescent↗

Skin virulence of attenuated pseudorabies virus (PRV) strains.

After intradermal inoculation of the attenuated pseudorabies virus (PRV) strains, Bartha, MK35 (gI+) and MK35-T-2 (gI-) to rabbits, they caused local inflammatory nodules with oedema reddiness and necrosis. The specifity of these reactions was confirmed by their inhibition with anti-PRV serum. The minimal dose that caused visible skin reaction was about 10(2) TCID50/ml for Bartha and MK35-T-2 (gI-) strains and over 10(4) TCID50/ml for the MK35 (gI+) strain. It is assumed that the established residual skin virulence can serve as an additional distinction marker for attenuated PRV strains.

Animals↗