49 results on '"Krenacs L"'
Search Results
2. Rare provisional entity: primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma in a young woman
- Author
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Csomor, J., Bognar, A., Benedek, S., Sinko, J., Fekete, S., Krenacs, L., Matolcsy, A., and Reiniger, L.
- Subjects
Cutaneous T cell lymphoma -- Case studies ,CD8 lymphocytes -- Physiological aspects ,Health - Published
- 2008
3. Platelet-derived growth factor receptor beta (PDGFRbeta) immunohistochemistry highlights activated bone marrow stroma and is potentially predictive for fibrosis progression in prefibrotic myeloproliferative neoplasia
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Mehes, G., Tzankov, A., Hebeda, K.M., Anagnostopoulos, I., Krenacs, L., Bedekovics, J., Mehes, G., Tzankov, A., Hebeda, K.M., Anagnostopoulos, I., Krenacs, L., and Bedekovics, J.
- Abstract
Item does not contain fulltext, AIMS: Myelofibrosis is the result of aberrant stromal activity which is determined routinely by reticulin staining in bone marrow biopsies. As matrix fibres are the product of activated fibroblasts, we analysed fibre accumulation compared to stromal cell activity during myelofibrosis progression using the fibroblast activation marker platelet-derived growth factor receptor beta (PDGFRbeta) by immunohistochemistry. METHODS AND RESULTS: Initial and follow-up bone marrow biopsies from 84 patients with myeloproliferative neoplasia, including 55 cases with primary myelofibrosis, were evaluated from five haematopathology centres. The stromal mass was measured by conventional reticulin staining [myelofibrosis (MF) grade, 0-3] and PDGFRbeta-positive cells using a novel PDGFRbeta scoring system (0-3). Results were correlated for prediction of progression. The MF grade and the PDGFRbeta score showed excellent correlation (Spearman's r = 0.83, P < 0.0001). Elevated PDGFRbeta scores (higher than MF-grade) predicted myelofibrosis progression in total with 43% sensitivity and 57% specificity, and short-term (within 1 year) progression with 82% sensitivity and 53% specificity. Progression of prefibrotic disease to manifest myelofibrosis could be forecast with 90% sensitivity and 75% specificity. CONCLUSION: PDGFRbeta highlights stromal cell activation in marrow fibrosis, which is closely related to matrix accumulation, indicating a direct clinical impact especially in prefibrotic myeloproliferative disorders.
- Published
- 2015
4. Analysis of immunoglobulin H gene rearrangement by polymerase chain reaction in primary central nervous system lymphoma
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Kros, J.M., Bagdi, E, Zheng, Pingpin, Hop, Driesse, MJ (Maarten), Krenacs, L, Dinjens, Winand, Pathology, Epidemiology, and Neurosurgery
- Published
- 2002
5. Cytotoxic granular protein expression, Epstein-Barr virus strain type, and latent membrane protein-1 oncogene deletions in nasal T-lymphocyte/natural killer cell lymphomas from Mexico
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Kojo Elenitoba-Johnson, Zarate-Osorno A, Meneses A, Krenacs L, Dw, Kingma, Raffeld M, and Es, Jaffe
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Adult ,Male ,Pore Forming Cytotoxic Proteins ,Herpesvirus 4, Human ,Membrane Glycoproteins ,Adolescent ,Perforin ,Nose Neoplasms ,Membrane Proteins ,Proteins ,RNA-Binding Proteins ,Middle Aged ,Lymphoma, T-Cell ,Immunohistochemistry ,Poly(A)-Binding Proteins ,Polymerase Chain Reaction ,T-Cell Intracellular Antigen-1 ,Killer Cells, Natural ,Viral Matrix Proteins ,Humans ,Female ,Mexico ,Gene Deletion ,In Situ Hybridization ,Aged - Abstract
Nasal T-lymphocyte/natural killer cell lymphomas (nT/NKLs) are a distinct group of neoplasms highly associated with Epstein-Barr virus (EBV), with a high prevalence in Asia but rare in Western countries. Recent studies indicate that these neoplasms are of cytotoxic T- or NK-cell derivation. Previous studies identifying a characteristic 30-base pair deletion within the 3' end of latent membrane protein-1 (del-LMP-1) in other EBV-associated lymphomas suggested a pathogenetic role for del-LMP-1 in those neoplasms. We examined 23 cases of nT/NKL from Mexico for expression of the cytolytic granular proteins TIA-1 and perforin (PRF), and for the presence of EBV by in situ hybridization (ISH). Polymerase chain reaction was performed to identify the EBV (EBNA-2) strain type and the status of the LMP-1 gene (del-LMP-1). Controls consisted of 11 sinonasal B-cell lymphomas (nBLs) and 30 reactive tonsils (RTs) from healthy Mexican individuals. The nT/NKLs expressed TIA-1 in 21 (91%) of 23 cases and PRF in 15 (65%) of 23 cases. In contrast, all of the nBLs were negative for TIA-1 and PRF. Twenty-two (96%) of 23 nT/NKLs were positive for EBV by ISH. In contrast, only 2 (18%) of 11 nBLs were positive for EBV by ISH. EBV strain Type A was identified in 21 (91%) of 23 cases, whereas strain Type B was present in 2 (9%) of the 23 nT/NKLs. A similar percentage (80%) of Type A was noted in 12 of the 15 RTs. del-LMP-1 was detected in 6 (26%) of 23 nT/NKLs, comprising 4 cases of Type A and 2 of Type B. del-LMP-1 was detected in 9 (45%) of 20 RTs. Our results indicated that TIA-1 and PRF were sensitive markers of nT/NKL. The presence of del-LMP-1 in comparable frequencies in the RTs and nT/NKLs suggested to us that this genotype was common in the Mexican population and argued against a definite pathogenetic role for del-LMP-1 in nT/NKL.
- Published
- 1998
6. Localization of the cell proliferation and apoptosis-associated CAS protein in lymphoid neoplasms
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Wellmann A, Krenacs L, thierry fest, Scherf U, Pastan I, Raffeld M, and Brinkmann U
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Lymphoma ,Staining and Labeling ,Palatine Tonsil ,Proteins ,Apoptosis ,Immunohistochemistry ,humanities ,eye diseases ,Cellular Apoptosis Susceptibility Protein ,embryonic structures ,Humans ,human activities ,Microtubule-Associated Proteins ,Cell Division ,Research Article - Abstract
We have evaluated the expression and distribution of the cellular apoptosis susceptibility (CAS) protein in normal lymphoid tissue and malignant lymphomas. CAS protein, the product of the CAS gene, is associated with microtubules and the mitotic spindle. Immunohistochemistry with an antibody to CAS shows many CAS-positive cells in normal tonsils. The majority of strongly CAS-positive cells were localized to the dark zone of the follicles, whereas the mantle zone and interfollicular areas were essentially negative. Double staining for CAS and Ki-67 revealed co-expression of the two proliferation markers in approximately 85 to 90% of the CAS-positive cells. Different subtypes of lymphomas exhibited varying patterns of CAS expression. Low-grade non-Hodgkin's lymphoma generally revealed weak staining with CAS, with 10 to 60% of all cells being positive. In contrast, highly malignant non-Hodgkin's lymphoma and malignant cells of Hodgkin's disease displayed very strong CAS positivity, with staining of up to 80% of the atypical cells. Overall, the staining pattern of CAS and Ki-67 was superimposable within a particular lymphoma subtype. However, in all lymphomas we observed a significant fraction of CAS-positive normal and malignant lymphocytes that were Ki-67 negative, probably because they were momentarily noncycling cells. We conclude that a high expression of CAS correlates with proliferation of normal and malignant lymphoid cells. The fact that detection of CAS protein identifies a higher portion of proliferating and malignant cells than Ki-67 warrants further evaluation of CAS protein as a marker with a diagnostic potential.
- Published
- 1997
7. Rare provisional entity: primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma in a young woman
- Author
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Csomor, J, primary, Bognar, A, additional, Benedek, S, additional, Sinko, J, additional, Fekete, S, additional, Krenacs, L, additional, Matolcsy, A, additional, and Reiniger, L, additional
- Published
- 2007
- Full Text
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8. Refractory sprue: Report of 2 cases without previous history of celiac disease
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Gurbity Palfi, T, primary, Krenacs, L, additional, Bagdi, E, additional, Krenacs, T, additional, Piukovics, K, additional, and Kiss, J, additional
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- 2004
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9. The serine protease granzyme M is preferentially expressed in NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity
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Krenacs, L., primary
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- 2002
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10. Panniculitis-like T-cell lymphoma clinically manifested as alopecia
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Torok, L., primary, Gurbity, T.P., additional, Kirschner, A., additional, and Krenacs, L., additional
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- 2002
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11. Effects of long-term low-dose mifepristone on reproductive function in women
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Croxatto, H. B., primary, Kovacs, L., additional, Massai, R., additional, Resch, B. A., additional, Fuentealba, B., additional, Salvatierra, A. M., additional, Croxatto, H. D., additional, Zalanyi, S., additional, Viski, S., additional, and Krenacs, L., additional
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- 1998
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12. Classification of T-cell and NK-cell neoplasms based on the REAL classification
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Jaffe, E.S., primary, Krenacs, L., additional, and Raffeld, M., additional
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- 1997
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13. Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin
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Cooke, CB, primary, Krenacs, L, additional, Stetler-Stevenson, M, additional, Greiner, TC, additional, Raffeld, M, additional, Kingma, DW, additional, Abruzzo, L, additional, Frantz, C, additional, Kaviani, M, additional, and Jaffe, ES, additional
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- 1996
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14. An antiserum reacts with an evolutionary conserved region in the ε subunit of the T-cell receptor—CD3 complex in phylogenetically distant species
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Kurucz, E., primary, Glavits, R., additional, Krenacs, L., additional, Krenacs, T., additional, Ocsovszky, I., additional, Keresztes, G., additional, Monostori, E., additional, and Ando, I., additional
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- 1993
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15. 45 High frequency and prognostic importance of autoimmune hemolytic anemia in splenic marginal zone lymphoma
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Fodor, A., Hoffer, I., Krenács, L., Bagdi, E., Csomor, J., Matolcsy, A., Molnár, M.Z., Eid, H., Nagy, Z., and Demeter, J.
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- 2010
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16. O24 Immunological role of pathological phenotype in peripheral T-cell lymphoma
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Krenács, L. and Bagdi, E.
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- 2007
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17. An anti-CD3e serum detects T lymphocytes in paraffin-embedded pathological tissues in many animal species
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Keresztes, G., Glavits, R., Krenacs, L., Kurucz, E., and Ando, I.
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- 1996
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18. A tumor suppressor function for NFATc3 in T cell lymphomagenesis by murine leukemia virus
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Andrulis, M., Sys Zoffmann Glud, Annette Sorensen, Wang, B., Kondo, E., Randi Jessen, Krenacs, L., Stelkovics, E., Wabl, M., Serfling, E., Palmetshofer, A., and Finn Skou Pedersen
19. Hepatosplenic T-Cell Lymphoma: A Distinct Clinicopathologic Entity of Cytotoxic γδ T-Cell Origin
- Author
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Cooke, C.B., Krenacs, L., Stetler-Stevenson, M., Greiner, T.C., Raffeld, M., Kingma, D.W., Abruzzo, L., Frantz, C., Kaviani, M., and Jaffe, E.S.
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- 1996
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20. An antiserum reacts with an evolutionary conserved region in the e subunit of the T-cell receptor-CD3 complex in phylogenetically distant species
- Author
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Kurucz, E., Glavits, R., Krenacs, L., and Krenacs, T.
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- 1993
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21. Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma.
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Finalet Ferreiro J, Rouhigharabaei L, Urbankova H, van der Krogt JA, Michaux L, Shetty S, Krenacs L, Tousseyn T, De Paepe P, Uyttebroeck A, Verhoef G, Taghon T, Vandenberghe P, Cools J, and Wlodarska I
- Subjects
- ATP Binding Cassette Transporter, Subfamily B genetics, ATP Binding Cassette Transporter, Subfamily B metabolism, Adolescent, Adult, Child, Chimerin Proteins metabolism, Chromosome Mapping, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Loci, Genome, Human, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, Lymphoma, T-Cell metabolism, Lymphoma, T-Cell pathology, Male, Microfilament Proteins metabolism, Middle Aged, Neoplasm Proteins metabolism, Nerve Tissue Proteins metabolism, Splenic Neoplasms metabolism, Splenic Neoplasms pathology, Transcriptome, Chimerin Proteins genetics, Chromosome Aberrations, Chromosomes, Human, Pair 7, Liver Neoplasms genetics, Lymphoma, T-Cell genetics, Microfilament Proteins genetics, Neoplasm Proteins genetics, Nerve Tissue Proteins genetics, Splenic Neoplasms genetics
- Abstract
Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six i(7)(q10)-positive HSTL cases, including HSTL-derived cell line (DERL-2), and three cases with ring 7 [r(7)], the recently identified rare variant aberration. Using high resolution array CGH, we profiled all cases and mapped the common deleted region (CDR) at 7p22.1p14.1 (34.88 Mb; 3506316-38406226 bp) and the common gained region (CGR) at 7q22.11q31.1 (38.77 Mb; 86259620-124892276 bp). Interestingly, CDR spans a smaller region of 13 Mb (86259620-99271246 bp) constantly amplified in cases with r(7). In addition, we found that TCRG (7p14.1) and TCRB (7q32) are involved in formation of r(7), which seems to be a byproduct of illegitimate somatic rearrangement of both loci. Further transcriptomic analysis has not identified any CDR-related candidate tumor suppressor gene. Instead, loss of 7p22.1p14.1 correlated with an enhanced expression of CHN2 (7p14.1) and the encoded β2-chimerin. Gain and amplification of 7q22.11q31.1 are associated with an increased expression of several genes postulated to be implicated in cancer, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any disease-defining mutation or gene fusion. Thus, chromosome 7 imbalances remain the only driver events detected in this tumor. We hypothesize that the Δ7p22.1p14.1-associated enhanced expression of CHN2/β2-chimerin leads to downmodulation of the NFAT pathway and a proliferative response, while upregulation of the CGR-related genes provides growth advantage for neoplastic δγT-cells and underlies their intrinsic chemoresistance. Finally, our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies.
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- 2014
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22. Unusual endoscopic appearance of Crohn's disease: another face of a multifaceted disease.
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Farkas K, Lazar G, Tiszlavicz L, Krenacs L, Nagy F, Szepes Z, Wittmann T, and Molnár T
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- Adult, Female, Humans, Prognosis, Cecum pathology, Colon pathology, Colonoscopy, Crohn Disease diagnosis, Endoscopy, Digestive System
- Published
- 2012
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23. Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease.
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Zuern C, Krenacs L, Starke S, Heimrich J, Palmetshofer A, Holtmann B, Sendtner M, Fischer T, Galle J, Wanner C, and Seibold S
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- Animals, Cardiomegaly blood, Cardiomegaly genetics, Cardiomegaly metabolism, Carrier Proteins genetics, Cell Growth Processes physiology, Fibroblasts pathology, Immunohistochemistry, Lymphoma, B-Cell, Marginal Zone blood, Lymphoma, B-Cell, Marginal Zone genetics, Lymphoma, B-Cell, Marginal Zone metabolism, Lymphoproliferative Disorders blood, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders metabolism, Mice, Mice, Knockout, Skin pathology, Tumor Suppressor Proteins genetics, Cardiomegaly pathology, Lymphoma, B-Cell, Marginal Zone pathology, Lymphoproliferative Disorders pathology, Tumor Suppressor Proteins deficiency
- Abstract
The microtubule associated tumor suppressor gene 1 (MTUS1) is a recently published tumor suppressor gene, which has also been shown to act as an early component in the growth inhibitory signaling cascade of the angiotensin II type 2 receptor (AT2R). In this study we report the generation of MTUS1 knock-out (KO) mice, which develop normally but reveal higher body weights and slightly decreased blood pressure levels. Twenty-eight percent of the studied MTUS1 KO mice also developed heart hypertrophy and 12% developed nephritis, independent of blood pressure levels. Forty-three percent of the MTUS1 KO mice revealed lymphoid hyperplasia affecting spleen (20%), kidney (37%), lung (23%), lymph nodes (17%), and liver (17%) accompanied with leukocytosis, lymphocytosis, and mild anemia. One animal (3%) developed a marginal zone B-cell lymphoma affecting submandibular salivary gland and regional lymph nodes. The symptoms of all mentioned animals are consistent with a B-cell lymphoproliferative disease with features of systemic lupus erythematosus. In addition, body weight of the MTUS1 KO mice was significantly increased and isolated skin fibroblasts showed increased cell proliferation and decreased cell size, compared to wild-type (WT) fibroblasts in response to depleted FCS concentration and lack of growth factors. In conclusion we herein report the first generation of a MTUS1 KO mouse, developing spontaneous heart hypertrophy and increased cell proliferation, confirming once more the anti-proliferative effect of MTUS1, and a SLE-like lymphoproliferative disease suggesting crucial role in regulation of inflammation. These MTUS1 KO mice can therefore serve as a model for further investigations in cardiovascular disease, autoimmune disease and carcinogenesis.
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- 2012
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24. Multiple antigen immunostaining procedures.
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Krenacs T, Krenacs L, and Raffeld M
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- Animals, Antibodies analysis, Antibodies immunology, Antigens immunology, Cervix Uteri ultrastructure, Chemical Precipitation, Connexin 43 analysis, Connexin 43 immunology, Cross Reactions, Epithelium chemistry, Epithelium ultrastructure, Female, Fluorescent Dyes, Humans, Keratin-19 analysis, Keratin-19 immunology, Microscopy methods, Antigens analysis, Fluorescent Antibody Technique methods, Immunoenzyme Techniques methods, Staining and Labeling methods
- Abstract
Detection of multiple antigens in the same tissue section can be done by combining a range of immunohisto/cytochemical techniques based either on light microscopic chromogenic precipitates or fluorochrome labeling. Light microscopic techniques preferred for this purpose use combinations of immunogold silver staining (black precipitate), immunoperoxidase, immunoalkaline phosphatase and immunogalactosidase methods using chromogens of different colors. Fluorochrome labels favored for these combinations include AMCA (blue), FITC (green), rhodamine (orange-red) and Cy5 (far red), their matching synthetic members from the Alexa series, or quantum dots. Antibodies directly labeled or those from noncross-reacting animal species (e.g., mouse, rabbit, goat, guinea pig etc.) can be applied simultaneously. When the antigens of interest are in separate cells or cell compartments (e.g., in cell membrane, cytoplasm or nucleus), and only cross-reacting antibodies are available, there have also been ways of avoiding unwanted cross-talk. These include the exploitation of the shielding effect of chromogens; inactivation of immuno-sequences of the first staining by using either acidic elution, formaldehyde fixation or microwave heating; combining unlabeled and hapten-labeled antibodies; or using labeled monovalent F(ab) secondary antibodies. In this chapter we briefly discuss the principle of multiple antigen immunolabeling and provide useful protocols for its performance.
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- 2010
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25. Heat-induced antigen retrieval for immunohistochemical reactions in routinely processed paraffin sections.
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Krenacs L, Krenacs T, Stelkovics E, and Raffeld M
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- Animals, Antigens, CD34 analysis, Buffers, Epitopes analysis, Hot Temperature, Humans, Microwaves, Palatine Tonsil chemistry, Palatine Tonsil ultrastructure, Pressure, T-Lymphocytes cytology, Antigens analysis, Immunohistochemistry methods, Paraffin Embedding methods
- Abstract
The development of heat-induced antigen (epitope) retrieval (HIER) technologies has led to dramatic improvements in our ability to detect antigens in formalin fixed, archival tissues. Paradoxically, wet heat treatment at temperatures greater than 95 degrees C in appropriate buffer solutions can reconstitute the antigenicity of many proteins that have been rendered nonreactive during the fixation and paraffin embedding process, which heretofore could only be identified in fresh or frozen tissues. The reason for this effect is unclear, but it has been suggested that the vigorous heat treatment partially reverses or disrupts the aldehyde cross-links occurring in proteins during formalin fixation and restores the original conformation of antigenic epitopes. The great success of antigen/epitope retrieval technologies further emphasizes the importance of preanalytical steps in immunohistochemistry. Over the past several years, since this technology was first reported, there have been numerous modifications to the original formulation. It is the purpose of this chapter to discuss the critical issues required for optimal HIER and to provide guidelines for the use of popular HIER buffers and heating devices used for routine immunohistochemical detection.
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- 2010
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26. Autoimmune hemolytic anemia as a risk factor of poor outcome in patients with splenic marginal zone lymphoma.
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Fodor A, Molnar MZ, Krenacs L, Bagdi E, Csomor J, Matolcsy A, and Demeter J
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- Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, L-Lactate Dehydrogenase blood, Lymphoma, B-Cell, Marginal Zone therapy, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Serum Albumin metabolism, Splenectomy, Splenic Neoplasms therapy, Anemia, Hemolytic, Autoimmune diagnosis, Anemia, Hemolytic, Autoimmune etiology, Lymphoma, B-Cell, Marginal Zone complications, Lymphoma, B-Cell, Marginal Zone diagnosis, Splenic Neoplasms complications, Splenic Neoplasms diagnosis
- Abstract
Splenic marginal zone lymphoma is a rare disease, accounting for 1% of all lymphomas. We reviewed our single center experience of 13 patients with splenic marginal zone lymphoma (SMZL). Based on the prognostic model developed by Intergruppo Italiano Linfomi, 31% (4/13) of our patients had good, 38% (5/13) had intermediate and 31% (4/13) had a poor prognosis. The presence of two out of three prognostic factors (anemia, elevated LDH, low serum albumin) assignes the patient into the high risk category. In patients with anemia and an elevated LDH due to hemolysis, the outcome seems to be especially poor. Three out of 13 (23%) cases were complicated by autoimmune hemolytic anemia. All patients with autoimmune hemolytic anaemia (AIHA) died 7-28 months after the diagnosis. The mean follow-up time of those nine patients who are still alive is longer than 5 years (36-100 months). Patients with AIHA had significantly (p < 0.001) worse survival than those without AIHA. The main finding of our study is that the presence of AIHA is an adverse prognostic factor in SMZL.
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- 2009
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27. Epigenetic changes and suppression of the nuclear factor of activated T cell 1 (NFATC1) promoter in human lymphomas with defects in immunoreceptor signaling.
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Akimzhanov A, Krenacs L, Schlegel T, Klein-Hessling S, Bagdi E, Stelkovics E, Kondo E, Chuvpilo S, Wilke P, Avots A, Gattenlöhner S, Müller-Hermelink HK, Palmetshofer A, and Serfling E
- Subjects
- Animals, DNA Methylation, Histones metabolism, Hodgkin Disease metabolism, Humans, Immunohistochemistry methods, Mice, Signal Transduction, Sp1 Transcription Factor metabolism, Transcription, Genetic, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, NFATC Transcription Factors genetics, Promoter Regions, Genetic
- Abstract
The nuclear factor of activated T cell 1 (Nfatc1) locus is a common insertion site for murine tumorigenic retroviruses, suggesting a role of transcription factor NFATc1 in lymphomagenesis. Although NFATc1 is expressed in most human primary lymphocytes and mature human T- and B-cell neoplasms, we show by histochemical stainings that NFATc1 expression is suppressed in anaplastic large cell lymphomas and classical Hodgkin's lymphomas (HLs). In HL cell lines, NFATc1 silencing correlated with a decrease in histone H3 acetylation, H3-K4 trimethylation, and Sp1 factor binding but with an increase in HP1 binding to the NFATC1 P1 promoter. Together with DNA hypermethylation of the NFATC1 P1 promoter, which we detected in all anaplastic large cell lymphoma and many HL lines, these observations reflect typical signs of transcriptional silencing. In several lymphoma lines, methylation of NFATC1 promoter DNA resulted in a "window of hypomethylation," which is flanked by Sp1-binding sites. Together with the under-representation of Sp1 at the NFATC1 P1 promoter in HL cells, this suggests that Sp1 factors can protect P1 DNA methylation in a directional manner. Blocking immunoreceptor signaling led to NFATC1 P1 promoter silencing and to a decrease in H3 acetylation and H3-K4 methylation but not DNA methylation. This shows that histone modifications precede the DNA methylation in NFATC1 promoter silencing.
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- 2008
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28. Optimization of PCR amplification for B- and T-cell clonality analysis on formalin-fixed and paraffin-embedded samples.
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Bereczki L, Kis G, Bagdi E, and Krenacs L
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- B-Lymphocytes metabolism, Clone Cells, DNA, Neoplasm genetics, False Negative Reactions, False Positive Reactions, Gene Rearrangement, B-Lymphocyte, Heavy Chain genetics, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor genetics, Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin Heavy Chains metabolism, Lymphoma, B-Cell genetics, Lymphoma, B-Cell metabolism, Lymphoma, B-Cell pathology, Lymphoma, T-Cell genetics, Lymphoma, T-Cell metabolism, Lymphoma, T-Cell pathology, Magnesium Chloride, Receptors, Antigen, T-Cell, gamma-delta genetics, Receptors, Antigen, T-Cell, gamma-delta metabolism, T-Lymphocytes metabolism, Taq Polymerase, Tissue Fixation, B-Lymphocytes pathology, Formaldehyde, Paraffin Embedding, Polymerase Chain Reaction methods, T-Lymphocytes pathology
- Abstract
In many cases, particularly in retrospective studies, only formalin-fixed and paraffin-embedded (FFPE) tissue samples are available for molecular studies. DNA recovered from FFPE tissues generally consists of fragmented small target sequences with chemical alterations. Clonality analysis is not easy on FFPE samples, in fact, it requires even more experience than that of performed on fresh samples or is more complicated than most genomic PCR amplifications for somatic genes. In our study, we have performed a multi-parameter PCR evaluation investigating immunoglobulin heavy chain gene (IgH) and T-cell receptor gamma gene (TCRgamma) rearrangements on non-purified crude lysates of FFPE samples, in order to establish the significance of different variables on performance of PCR amplification. The results showed that a slight decrease in the concentration of primers in combination with a slight increase in MgCl2 and Taq polymerase concentrations, as well as the use diluted crude template and a standard amount of dNTPs can be the modifications of choice while adjusting IgH and TCRgamma clonality tests on poor quality DNA FFPE samples. Using our improved protocol, 74% (17/23) of the tested B-cell lymphomas and 68% (31/46) of the tested T-cell lymphomas demonstrated monoclonal PCR product, proving the applicability of our optimized method. Our experience may be of help during the optimization process in technically difficult cases as well as to determine which parameters and how should be changed to minimize false-negative and false-positive results.
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- 2007
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29. Hepatosplenic gammadelta T-cell lymphoma with ring chromosome 7, an isochromosome 7q equivalent clonal chromosomal aberration.
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Tamaska J, Adam E, Kozma A, Gopcsa L, Andrikovics H, Tordai A, Halm G, Bereczki L, Bagdi E, and Krenacs L
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow chemistry, Bone Marrow pathology, Clone Cells, DNA, Neoplasm analysis, Fatal Outcome, Female, Humans, Immunophenotyping, In Situ Hybridization, Fluorescence, Liver Neoplasms chemistry, Liver Neoplasms drug therapy, Liver Neoplasms genetics, Lymphoma, T-Cell chemistry, Lymphoma, T-Cell drug therapy, Lymphoma, T-Cell genetics, Middle Aged, Polymerase Chain Reaction, Spectral Karyotyping, Splenic Neoplasms chemistry, Splenic Neoplasms drug therapy, Splenic Neoplasms genetics, Chromosome Aberrations, Chromosomes, Human, Pair 7, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, Liver Neoplasms pathology, Lymphoma, T-Cell pathology, Splenic Neoplasms pathology
- Abstract
Hepatosplenic T-cell lymphoma is a rare, clinically aggressive lymphoma. Most cases represent a neoplasm of mature non-activated gammadelta T cells. Isochromosome 7q i(7)(q10) is thought to be the primary cytogenetic abnormality of this disease. In this paper, we describe a hepatosplenic gammadelta T-cell lymphoma case, with clonal ring chromosome 7 exemplifying an isochromosome 7q equivalent clonal aberration. A 62-year-old female patient presented with thrombocytopenia, isolated hepatosplenomegaly, and extremely high levels of LDH. Bone marrow work-up demonstrated a sinusoidal cytotoxic T-cell infiltrate with blastic features, while molecular studies verified monoclonal rearrangement for both TCR gamma and TCR delta genes. Cytogenetics revealed clonal abnormalities including ring chromosome 7, trisomy 8, and der(19), while FISH analysis detected 7q amplification with partial deletion of 7p in ring chromosome 7. To the best of our knowledge, this is the first reported T-cell lymphoma case with ring chromosome 7.
- Published
- 2006
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30. Phenotype of neoplastic cells in angioimmunoblastic T-cell lymphoma is consistent with activated follicular B helper T cells.
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Krenacs L, Schaerli P, Kis G, and Bagdi E
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- Humans, Lymphocyte Activation, Phenotype, Immunoblastic Lymphadenopathy pathology, Lymphoma, T-Cell pathology, T-Lymphocytes, Helper-Inducer pathology
- Published
- 2006
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31. In differentiating prefusion myoblasts connexin43 gap junction coupling is upregulated before myoblast alignment then reduced in post-mitotic cells.
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Gorbe A, Becker DL, Dux L, Krenacs L, and Krenacs T
- Subjects
- Animals, Blotting, Western, Cell Differentiation, Cell Fusion, Cell Membrane chemistry, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Cyclin-Dependent Kinase Inhibitor p27 metabolism, Cytoplasm chemistry, Fluorescent Dyes analysis, Fluorescent Dyes metabolism, Microscopy, Confocal, Mitosis, Myoblasts metabolism, Rats, Up-Regulation, Connexin 43 analysis, Connexin 43 metabolism, Gap Junctions, Myoblasts chemistry, Myoblasts cytology
- Abstract
Previously we have shown that during in vivo muscle regeneration differentiating rat primary myoblasts transiently upregulate connexin43 (Cx43) gap junctions and leave cell cycle synchronously. Here, we studied the temporal regulation of Cx expression in relation to functional dye coupling in allogenic primary myoblast cultures using western blotting, immuno-confocal microscopy and dye transfer assays. As in vivo, Cx43 was the only Cx isotype out of Cx26, 32, 37, 40, 43 and 45 found in cultured rat myoblasts by immunostaining. Cultured myoblasts showed similar temporal regulation of Cx43 expression and phenotypic maturation to those regenerating in vivo. Cx43 protein was progressively upregulated in prefusion myoblasts, first by the cytoplasmic assembly in sparse myoblast meshworks and then in cell membrane particles in aligned cells. Dye injection using either Lucifer Yellow alone, Cascade Blue with a non-junction permeant FITC-dextran revealed an extensive gap junction coupling between the sparse interacting myoblasts and a reduced communication between the aligned, but still prefused cells. The aligned myoblasts, uniformly upregulate p21(waf1/cip1) and p27(kip1) cell cycle control proteins. Taken together, in prefusion myoblasts less membrane-bound Cx43 was found to mediate substantially more efficient dye coupling in the growing cell fraction than those in the aligned post-mitotic myoblasts. These and our in vivo results in early muscle differentiation are consistent with the role of Cx43 gap junctions in synchronizing cell cycle control of myoblasts to make them competent for a coordinated syncytial fusion.
- Published
- 2006
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32. A tumor-suppressor function for NFATc3 in T-cell lymphomagenesis by murine leukemia virus.
- Author
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Glud SZ, Sørensen AB, Andrulis M, Wang B, Kondo E, Jessen R, Krenacs L, Stelkovics E, Wabl M, Serfling E, Palmetshofer A, and Pedersen FS
- Subjects
- Animals, Leukemia Virus, Murine genetics, Leukemia, Experimental genetics, Leukemia, Experimental pathology, Lymphoma, T-Cell genetics, Lymphoma, T-Cell immunology, Lymphoma, T-Cell pathology, Mice, Mice, Inbred BALB C, NFATC Transcription Factors deficiency, NFATC Transcription Factors genetics, Retroviridae Infections genetics, Retroviridae Infections pathology, Tumor Suppressor Proteins genetics, Tumor Virus Infections genetics, Tumor Virus Infections pathology, Virus Integration immunology, Leukemia Virus, Murine immunology, Leukemia, Experimental immunology, NFATC Transcription Factors immunology, Retroviridae Infections immunology, Tumor Suppressor Proteins immunology, Tumor Virus Infections immunology
- Abstract
Nuclear factor of activated T cell (NFAT) transcription factors play a central role in differentiation, activation, and elimination of lymphocytes. We here report on the finding of provirus integration into the Nfatc3 locus in T-cell lymphomas induced by the murine lymphomagenic retrovirus SL3-3 and show that NFATc3 expression is repressed in these lymphomas. The provirus insertions are positioned close to the Nfatc3 promoter or a putative polyadenylated RNA (polyA) region. Furthermore, we demonstrate that NFATc3-deficient mice infected with SL3-3 develop T-cell lymphomas faster and with higher frequencies than wild-type mice or NFATc2-deficient mice. These results identify NFATc3 as a tumor suppressor for the development of murine T-cell lymphomas induced by the retrovirus SL3-3.
- Published
- 2005
- Full Text
- View/download PDF
33. Transient upregulation of connexin43 gap junctions and synchronized cell cycle control precede myoblast fusion in regenerating skeletal muscle in vivo.
- Author
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Gorbe A, Becker DL, Dux L, Stelkovics E, Krenacs L, Bagdi E, and Krenacs T
- Subjects
- Animals, Cell Cycle Proteins analysis, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Desmin analysis, Elapid Venoms pharmacology, Gap Junctions chemistry, Gap Junctions ultrastructure, Immunohistochemistry, Ki-67 Antigen analysis, Microscopy, Electron, Muscle Fibers, Skeletal chemistry, Muscle Fibers, Skeletal physiology, Muscle Fibers, Skeletal ultrastructure, Muscle, Skeletal chemistry, Muscle, Skeletal ultrastructure, Myoblasts chemistry, Rats, Rats, Wistar, Regeneration drug effects, Time Factors, Tumor Suppressor Proteins analysis, Up-Regulation, Cell Cycle physiology, Connexin 43 analysis, Muscle, Skeletal physiology, Myoblasts physiology, Regeneration physiology
- Abstract
The spatio-temporal expression of gap junction connexins (Cx) was investigated and correlated with the progression of cell cycle control in regenerating soleus muscle of Wistar rats. Notexin caused a selective myonecrosis followed by the complete recapitulation of muscle differentiation in vivo, including the activation, commitment, proliferation, differentiation and fusion of myogenic cells. In regenerating skeletal muscle, only Cx43 protein, out of Cx-s 26, -32, -37, -40, -43 and -45, was detected in desmin positive cells. Early expression of Cx43 in the proliferating single myogenic progenitors was followed by a progressive upregulation in interacting myoblasts until syncytial fusion, and then by a rapid decline in multinucleate myotubes. The significant upregulation of Cx43 gap junctions in aligned myoblasts preceding fusion was accompanied by the widespread nuclear expression of cyclin-dependent kinase inhibitors p21(waf1/Cip1) and p27(kip1) and the complete loss of Ki67 protein. The synchronized exit of myoblasts from the cell cycle following extensive gap junction formation suggests a role for Cx43 channels in the regulation of cell cycle control. The potential of Cx43 channels to stimulate p21(waf1/Cip1) and p27(kip1) is known. In the muscle, proving the involvement of Cx43 in either a direct or a bystander cell cycle regulation requires functional investigations.
- Published
- 2005
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34. Low level of cyclin D1 protein expression in thyroid microcarcinomas from an autopsy series.
- Author
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Kovacs GL, Stelkovics E, Krenacs L, Gonda G, Goth M, Kovacs L, Gorombey Z, Hubina E, and Szabolcs I
- Subjects
- Adult, Aged, Carcinoma, Papillary epidemiology, Carcinoma, Papillary pathology, Female, Histocytochemistry, Humans, Hungary epidemiology, Male, Middle Aged, Prevalence, Thyroid Neoplasms epidemiology, Thyroid Neoplasms pathology, Carcinoma, Papillary metabolism, Cyclin D1 biosynthesis, Thyroid Neoplasms metabolism
- Abstract
In a recent epidemiological screening study in an autopsy series, we found a high prevalence of microcarcinomas (MCs) (21/443 = 4.74%). We found no iodine intake-, gender-, or age-dependent differences in the prevalence of MCs. The results suggest a different and benign behavior of MCs compared to clinical cancer. The role of cyclin D1 overexpression in the pathogenesis of thyroid tumors is not known clearly; however, overexpression of this protein was reported in well-differentiated papillary cancers and in incidentally found metastasizing MCs. To date, cyclin D1 expression has not been investigated in autopsy-derived thyroid MCs. Eight MCs were available for immunostaining and comparison with 15 clinically detected papillary thyroid cancers. Fourteen out of 15 clinical carcinomas expressed cyclin D1 (93.3%), while in the MCs this ratio was 1 out of 8 (12.5%) (p = 0.0001). The only cyclin D1-positive MC was multifocal (both lobes of the gland were affected). We concluded that the benign behavior of most autopsy-derived MCs may be associated with the lack of cyclin D1 overexpression.
- Published
- 2005
- Full Text
- View/download PDF
35. Increased sensitivity of B-cell clonality analysis in formalin-fixed and paraffin-embedded B-cell lymphoma samples using an enzyme blend with both 5'-->3' DNA polymerase and 3'-->5' exonuclease activity.
- Author
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Gurbity TP, Bagdi E, Groen NA, Budel LM, Abbou M, Krenacs L, and Dinjens WN
- Subjects
- DNA Primers, Exonucleases, Formaldehyde, Gene Rearrangement, B-Lymphocyte, Genes, Immunoglobulin, Humans, Paraffin Embedding, Retrospective Studies, Sensitivity and Specificity, DNA, Neoplasm analysis, DNA-Directed DNA Polymerase, Lymphoma, B-Cell genetics, Polymerase Chain Reaction methods
- Abstract
Polymerase chain reaction (PCR)-based detection of immunoglobulin heavy chain (IgH) gene rearrangement for determination of B-cell clonality needs to be simple but optimally sensitive. Efficient IgH PCR analysis can be hampered by sequence variability in the template DNA, despite of the use of degenerative primers. To improve sensitivity of the B-cell clonality analysis in formalin-fixed and paraffin-embedded (FFPE) tissues, we have performed framework three-area (FR3)/joining gene (JH) IgH PCR utilizing an enzyme blend (r Tth DNA Polymerase, XL) providing both 5'-->3' polymerase and 3'-->5' exonuclease activities. The DNA samples were extracted from FFPE biopsies of 43 mature B-cell lymphoma cases of so-called germinal center and post-germinal center origin, including 6 nodal follicular lymphomas (FL), 15 gastric mucosa-associated lymphoid tissue (MALT) lymphomas, and 22 gastric diffuse large B-cell lymphomas (DLBCL). Of the cases, 31 (17 DLBCL and 14 MALT lymphoma) represented small endoscopic biopsies. Serial dilutions of target DNA were applied to avoid inconsistent bands that may be seen when the input amount of template is too low, which can be the case when DNA is extracted from FFPE endoscopic gastric biopsies. Using conventional Taq polymerase, consistent monoclonal product was found in 53% (23/43) of the cases (FL: 67%; MALT lymphoma: 47%; DLBCL: 55%). The r Tth polymerase showed reproducible monoclonal pattern in 72% (31/43) of the cases (FL: 67%; MALT lymphoma: 73%; DLBCL: 73%); the sensitivity is compatible with one that can be detected with conventional FR3/JH PCR in fresh/frozen tissues. In conclusion, the r Tth DNA polymerase greatly improves sensitivity of FR3/JH PCR in FFPE biopsies of mature B-cell lymphomas, most probably by increasing the primer matches during PCR amplification.
- Published
- 2003
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- View/download PDF
36. Classification of cytotoxic T-cell and natural killer cell lymphomas.
- Author
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Jaffe ES, Krenacs L, and Raffeld M
- Subjects
- Cell Lineage, Humans, Lymphoma, Non-Hodgkin pathology, Lymphoma, T-Cell, Peripheral, Killer Cells, Natural pathology, Lymphoma, Non-Hodgkin classification, T-Lymphocytes, Cytotoxic pathology
- Abstract
Mature or peripheral T-cell lymphomas are uncommon, accounting for only 10% to 15% of all non-Hodgkin's lymphomas. The classification of these neoplasms has been controversial. In contrast to B-cell lymphomas, cytologic features have not been useful in defining disease entities, and cytologic grade has not helped predict the clinical course. Similarly, many entities of T-cell or natural killer (NK) cell derivation do not have a specific immunophenotype. Clinical features are of major importance in defining T-cell and NK cell neoplasms, and in some cases the clinical syndrome, may be more important than the precise cell of origin. The majority of cytotoxic T-cell and NK cell lymphomas arise in extranodal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Three major categories of extranodal T/NK cell tumors are recognized in the World Health Organization (WHO) classification: extranodal NK/T, nasal-type; enteropathy-type; and subcutaneous panniculitis-like. Epstein Barr virus (EBV) is closely linked to nasal NK/T-cell lymphoma, but shows geographic and racial variations in other subtypes. Tumors resembling the prototype of nasal NK/T-cell lymphoma occur in a variety of extranodal sites, and are referred to as nasal-type. Hepatosplenic T-cell lymphoma is a more systemic disease derived from functionally immature cytotoxic cells, usually gammadelta T-cell origin. Cytotoxic T-cell lymphomas of mature gammadelta T-cell origin most often arise in mucocutaneous sites, and may resemble the prototypes of extranodal T/NK cell lymphoma: nasal, enteropathy-associated, and panniculitis-like. Cytotoxic T/NK cell lymphomas occur with increased frequency in the setting of immune suppression, especially following organ transplantation. The nodal T-cell lymphoma most often exhibiting a cytotoxic immunophenotype is anaplastic large cell lymphoma (ALCL). Primary cutaneous ALCL frequently but not invariably expresses cytotoxic molecules. While the majority of extranodal neoplasms are derived from innate immune effector cells of NK cell and T-cell origin (gammadelta greater than alphabeta), most nodal cytotoxic T-cell lymphomas probably belong to the adaptive immune system. Studies of these neoplasms may assist in unraveling the diversity of their normal counterparts.
- Published
- 2003
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- View/download PDF
37. The serine protease granzyme M is preferentially expressed in NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity.
- Author
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Krenacs L, Smyth MJ, Bagdi E, Krenacs T, Kopper L, Rudiger T, Zettl A, Muller-Hermelink HK, Jaffe ES, and Raffeld M
- Subjects
- Cell Lineage, Granzymes, Humans, Immunity, Innate, Lymphoma, Large B-Cell, Diffuse enzymology, Mycosis Fungoides enzymology, Neoplastic Stem Cells enzymology, Sezary Syndrome enzymology, Intestinal Neoplasms enzymology, Killer Cells, Natural enzymology, Lymphoma, T-Cell enzymology, Neoplasm Proteins analysis, Nose Neoplasms enzymology, Receptors, Antigen, T-Cell, gamma-delta analysis, Serine Endopeptidases analysis
- Abstract
Granzyme M (GM) is a novel serine protease whose expression is highly restricted to natural killer (NK) cells, CD3(+)CD56(+) T cells, and gamma delta T cells. Using a GM-specific monoclonal antibody, we analyzed the expression of GM in 214 mature T-cell and NK-cell lymphomas. GM was preferentially expressed in nasal NK/T-cell lymphomas (100%), gamma delta T-cell lymphomas (100%), and intestinal T-cell lymphomas (85%). In contrast, GM expression was present at low prevalence in mycosis fungoides/Sézary syndrome (3%), anaplastic large-cell lymphoma (6%), panniculitis-like T-cell lymphoma (11%), and angioimmunoblastic T-cell lymphoma (0%) cases. Peripheral T-cell lymphomas of unspecified subtype showed an intermediate frequency (37%) of GM expression, consistent with their heterogeneous origin. We conclude that GM expression is a distinctive feature of the nasal NK/T-cell, gamma delta T-cell, and intestinal T-cell lymphomas, and suggest that these tumors develop from lymphocytes involved in innate immunity.
- Published
- 2003
- Full Text
- View/download PDF
38. Analysis of immunoglobulin H gene rearrangement by polymerase chain reaction in primary central nervous system lymphoma.
- Author
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Kros JM, Bagdi EK, Zheng P, Hop WC, Driesse MJ, Krenacs L, and Dinjens WN
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Central Nervous System Neoplasms mortality, Central Nervous System Neoplasms pathology, Female, Humans, Lymphoma, Non-Hodgkin mortality, Lymphoma, Non-Hodgkin pathology, Male, Middle Aged, Polymerase Chain Reaction, Retrospective Studies, Survival Analysis, Central Nervous System Neoplasms genetics, Gene Rearrangement, Immunoglobulins genetics, Lymphoma, Non-Hodgkin genetics
- Abstract
Object: Diagnosing primary central nervous system lymphoma (PCNSL) may be difficult either because of a paucity of tumor cells in the brain biopsy specimens or a failure to demonstrate monoclonality on immunomorphological studies. Monoclonality can also be demonstrated by amplification of the rearranged immunoglobulin H genes by polymerase chain reaction (PCR) to the framework region (FR)3 and FR2 complementarity determining region (CDR)-III and CDR-II of these genes. The PCR method is feasible with formalin-fixed, paraffin-embedded biopsy material and has proven to be helpful in the diagnosis of non-Hodgkin lymphoma on biopsy samples obtained from various locations in the body. Nevertheless, few studies have addressed the value of this method in the context of PCNSL. In the present study, the contribution of both FR3 single and FR2 seminested PCR procedures for confirming the diagnosis of PCNSL was estimated retrospectively in 30 cases of PCNSL and in three cases of epidural lymphoma., Methods: Twenty-eight cases of immunophenotypically confirmed PCNSL and two of suspected lymphoma were studied. Tissue specimens obtained in 22 cases of other cerebral diseases, among which were various inflammatory conditions. were used as negative controls. In 18 (60%) of 30 cases the results of FR3 PCR demonstrated monoclonality, whereas FR2 PCR showed monoclonality in 12 cases (40%). In 11 cases FR3 PCR yielded monoclonal patterns and FR2 PCR did not, whereas reversibly in five cases FR2 PCR proved monoclonality and FR3 PCR failed to do so. Adding the results of FR3 to those of FR2 PCR, monoclonal patterns were obtained in 23 (77%) of 30 cases. In both cases in which lymphoma was suspected but not proven immunomorphologically, FR3 PCR revealed monoclonality, as did FR2 PCR in one case. In all 22 control lesions either polyclonal patterns were seen or no consistent patterns were obtained. In the PCNSL group, older age of patients and multifocal presentation of lesions on neuroimaging were significantly associated with worse survival. No correlation between histological subtype and clinical outcome was elucidated., Conclusions: The application of FR3 and FR2 PCR is a useful additional tool in making the diagnosis of PCNSL. Moreover, in some cases the PCR method may be essential in distinguishing neoplasia from reactive conditions.
- Published
- 2002
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39. Follicular dendritic cells in reactive and neoplastic lymphoid tissues: a reevaluation of staining patterns of CD21, CD23, and CD35 antibodies in paraffin sections after wet heat-induced epitope retrieval.
- Author
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Bagdi E, Krenacs L, Krenacs T, Miller K, and Isaacson PG
- Subjects
- Antigens, CD immunology, Dendritic Cells, Follicular cytology, Dendritic Cells, Follicular metabolism, Epitopes analysis, Humans, Lymphoma diagnosis, Lymphoma pathology, Paraffin Embedding, Pseudolymphoma diagnosis, Pseudolymphoma pathology, Receptors, Complement 3b analysis, Receptors, Complement 3b immunology, Receptors, Complement 3d analysis, Receptors, Complement 3d immunology, Receptors, IgE analysis, Receptors, IgE immunology, Sarcoma diagnosis, Sarcoma pathology, Temperature, Tissue Fixation methods, Antigens, CD analysis, Dendritic Cells, Follicular immunology, Immunohistochemistry methods, Lymphoma immunology, Pseudolymphoma immunology, Sarcoma immunology
- Abstract
Structural alterations in the meshwork of follicular dendritic cells (FDCs) are frequently found in malignant lymphomas. Formaldehyde fixation and paraffin embedding, however, have long prevented consistent detection of FDCs. Wet heat-induced epitope retrieval in Dako Target Retrieval Solution (TRS) (pH 6.0) enabled the reliable detection of FDCs through CD21, CD23, and CD35 antigens in routinely processed tissues from 11 reactive and 69 neoplastic lymphoproliferations, thus allowing the distribution of the FDCs to be reevaluated. Germinal center FDCs in lymphoid hyperplasias and expanded FDC meshworks in the 8 mantle cell lymphomas, 7 low-grade MALT lymphomas, and 6 low-grade follicular lymphomas were intensely stained with all these markers. In 6 cases of B cell chronic lymphocytic leukemia, tumor cells were CD23+. In four cases of nodular lymphocyte predominance Hodgkin's disease (HD), expanded FDC meshwork's sharply delineating negative tumor cells and their rosetting T cell, were revealed mainly with the CD21 and CD35 antibodies. Follicular dendritic cells were also demonstrated in 11 cases of grade I nodular sclerosing HD, including follicular HD. Striking dendritic cell clusters were revealed with all 3 antibodies in 9 angioimmunoblastic T cell lymphomas. Sparse or no FDC meshworks were detected in the 4 cases of grade II nodular sclerosing HD, 5 follicular lymphomas with high-grade transformation, and 5 T cell-rich B cell lymphomas. CD35 immunostaining showed the most consistent labeling in the four FDC sarcomas studied in the current article. Reproducible demonstration of FDCs in routinely processed paraffin sections with CD21, CD23, and CD35 antibodies, as presented here, provides invaluable pieces of information in the diagnosis of lymphoproliferative disorders.
- Published
- 2001
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40. Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression.
- Author
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Quintanilla-Martinez L, Franklin JL, Guerrero I, Krenacs L, Naresh KN, Rama-Rao C, Bhatia K, Raffeld M, and Magrath IT
- Subjects
- Adolescent, Adult, Child, Female, Humans, Immunohistochemistry, Immunophenotyping, In Situ Hybridization, Killer Cells, Natural metabolism, Lymphoma, T-Cell epidemiology, Lymphoma, T-Cell metabolism, Lymphoma, T-Cell, Peripheral epidemiology, Lymphoma, T-Cell, Peripheral metabolism, Lymphoma, T-Cell, Peripheral pathology, Male, Middle Aged, Nose Neoplasms epidemiology, Nose Neoplasms metabolism, Peru, Prevalence, Tumor Suppressor Protein p53 metabolism, Killer Cells, Natural pathology, Lymphoma, T-Cell pathology, Nose Neoplasms pathology
- Abstract
Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus (EBV). These lymphomas are rare in Western populations and much more prevalent in some Asian and Latin American countries. Although there are several sizable studies from Asian countries, the same is not true from South America. The aim of this study was to analyze a series of 32 cases of nasal T-cell lymphoma from Peru and to further extend the characterization of this disease. Immunohistochemistry was performed on paraffin sections using the following antibodies: CD20 (L26), CD45RO, CD3, Ki67, CD57, CD56, TIA-1, bcl-2, and p53. The presence of EBV was investigated with immunohistochemical analysis for latent membrane protein (LMP)-1 and in situ hybridization using an antisense riboprobe to EBER 1. The 32 patients included 18 men and 14 women (M:F ratio, 1.2:1), with a median age of 43 years (11 to 72). Three categories were identified: (1) Nasal NK/T cell lymphomas (28 cases): The morphology ranged from small or medium-sized cells to large transformed cells. Necrosis was present in 86% of the cases, and angioinvasion was seen in 36% of the cases. All cases were positive for CD45RO, CD3, and for TIA-1. CD56 was positive in 21 of 27 cases (78%), and CD57 was negative in all cases. EBER 1 positivity was identified in most of the tumor cells in 27 of 28 cases (96%), including the six cases in which CD56 was negative. Overexpression of p53 was detected in 24 cases (86%). (2) Blastic NK cell lymphoma (1 case): The neoplastic cells resembled those of lymphoblastic lymphoma. CD56 and CD45RO were positive; TIA-1, TdT, and EBER-1 were negative. (3) Peripheral T-cell lymphoma (PTCL) unspecified (3 cases): CD56, TIA-1, and EBER-1 were negative. Nasal lymphomas from Peru with a T cell phenotype are predominantly EBV-associated NK/T cell lymphomas, similar to those described in Asian countries. The expression of CD56, TIA-1, and EBER-1, in combination, are very useful markers for the diagnosis of nasal NK/T cell lymphoma in paraffin-embedded tissue. The differential diagnosis of T-cell lymphomas in the nasal region should include rare cases of PTCL unspecified and the blastic variant of NK cell lymphoma. P53 is overexpressed in 86% of the cases. The significance of this finding with regard to clinical behavior and prognosis remains to be determined.
- Published
- 1999
- Full Text
- View/download PDF
41. Antigen retrieval for immunohistochemical reactions in routinely processed paraffin sections.
- Author
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Krenacs L, Krenacs T, and Raffeld M
- Subjects
- Humans, Microtomy, Paraffin Embedding, Antigens isolation & purification, Immunohistochemistry methods
- Published
- 1999
- Full Text
- View/download PDF
42. Primary nodal marginal zone lymphomas of splenic and MALT type.
- Author
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Campo E, Miquel R, Krenacs L, Sorbara L, Raffeld M, and Jaffe ES
- Subjects
- Adult, Aged, Biomarkers, Tumor analysis, DNA, Neoplasm analysis, Female, Humans, Immunophenotyping, Lymphoma, B-Cell chemistry, Lymphoma, B-Cell genetics, Lymphoma, B-Cell, Marginal Zone chemistry, Lymphoma, B-Cell, Marginal Zone genetics, Male, Middle Aged, Polymerase Chain Reaction, Retrospective Studies, Splenic Neoplasms chemistry, Splenic Neoplasms genetics, Lymph Nodes pathology, Lymphoma, B-Cell pathology, Lymphoma, B-Cell, Marginal Zone pathology, Splenic Neoplasms pathology
- Abstract
The existence of primary nodal marginal zone lymphomas (MZL) is controversial, as is their relationship to putative extranodal counterparts. Most nodal lymphomas with monocytoid B cell/marginal zone differentiation exhibit the morphologic and immunophenotypical characteristics of extranodal MALT-lymphomas. Splenic marginal zone lymphoma (SMZL) is also of putative marginal zone derivation, but it differs immunophenotypically from MALT lymphoma. To clarify the relationship between nodal and extranodal MZLs and to investigate the possible existence of a nodal variant of SMZL, 36 MZL initially considered to be primary nodal neoplasms were examined. Other low-grade lymphomas with marginal zone differentiation were excluded (small lymphocytic lymphoma/chronic lymphocytic leukemia [SLL/CLL], follicular lymphoma, and mantle cell lymphoma). Six nodal MZLs showed morphologic and phenotypic characteristics similar to those of SMZL, whereas 30 tumors were more similar to MALT-type lymphomas. The six tumors with SMZL features showed a polymorphic infiltrate surrounding residual germinal centers with absent or very attenuated mantle cuffs. These lymphomas were IgD positive (6/6) but cyclin D1 (0/5), CD5 (0/6), and CD23 (0/6) negative. Five of these patients came for treatment in stage I or II. No patient manifested splenomegaly, peripheral blood, and/or bone marrow infiltration either at diagnosis or during follow-up. Lymph nodes from 30 patients with MALT-type features showed a perisinusoidal and perivascular infiltration of monocytoid/centrocytoid cells and residual germinal centers with a relatively well-preserved mantle cuff. The neoplastic cells were negative for IgD (0/17), cyclin D1 (0/8), and CD5 (0/12). Seven of 16 (44%) patients with a detailed history and clinical follow-up had evidence of extranodal lymphoma. These observations suggest that most nodal B cell lymphomas with marginal zone differentiation are of the MALT type and that they are frequently associated with an extranodal component. In addition, a primary nodal counterpart of splenic MZL also exists, and may occur in the absence of splenomegaly.
- Published
- 1999
- Full Text
- View/download PDF
43. Multiple antigen immunostaining procedures.
- Author
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Krenacs T, Krenacs L, and Raffeld M
- Subjects
- Animals, Humans, Immunohistochemistry methods, Staining and Labeling methods
- Published
- 1999
- Full Text
- View/download PDF
44. Extranodal peripheral T-cell and NK-cell neoplasms.
- Author
-
Jaffe ES, Krenacs L, Kumar S, Kingma DW, and Raffeld M
- Subjects
- Humans, Killer Cells, Natural, Lymphoma, T-Cell epidemiology, World Health Organization, Lymphoma, T-Cell classification, Lymphoma, T-Cell pathology
- Abstract
Mature or peripheral T-cell lymphomas are uncommon, accounting for only 10% to 15% of all non-Hodgkin lymphomas, and their classification has been controversial. In contrast to B-cell lymphomas, cytologic features have not been useful in defining disease entities, and cytologic grade has not been useful in predicting the clinical course. Similarly, many entities of T-cell or NK-cell derivation do not have a specific immunophenotype. Clinical features are of major importance, sometimes more important than the precise cell of orgin, in defining T-cell and NK-cell neoplasms. Most extranodal T-cell/NK-cell lymphomas have a cytotoxic phenotpye. The expression of cytotoxic molecules may predispose to apoptosis by tumor cells and normal bystander cells. Three major categories of extranodal T/NK cell tumors are nasal, intestinal, and subcutaneous panniculitis-like. Hepatosplenic gamma delta T-cell lymphoma is a more systemic disease derived from functionally immature cytotoxic cells. Many extranodal T-cell and NK-cell neoplasms are associated with Epstein-Barr virus (EBV); the association seems site dependent and shows some geographic variation. Tumors resembling any of the 3 prototypes may occur in a variety of extranodal sites. Extranodal T/NK cell lymphomas occur with increased frequency in the setting of immune suppression, especially after organ transplantation.
- Published
- 1999
45. Transcription factor B-cell-specific activator protein (BSAP) is differentially expressed in B cells and in subsets of B-cell lymphomas.
- Author
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Krenacs L, Himmelmann AW, Quintanilla-Martinez L, Fest T, Riva A, Wellmann A, Bagdi E, Kehrl JH, Jaffe ES, and Raffeld M
- Subjects
- Antigens, CD20 analysis, Biomarkers, Tumor analysis, Cell Lineage, Cell Transformation, Neoplastic genetics, DNA-Binding Proteins genetics, Gene Expression Regulation, Neoplastic, Genes, Homeobox, Hematologic Neoplasms metabolism, Hematologic Neoplasms pathology, Hodgkin Disease metabolism, Hodgkin Disease pathology, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Lymphoma, B-Cell classification, Lymphoma, B-Cell pathology, Lymphoma, Follicular metabolism, Lymphoma, Follicular pathology, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, T-Cell metabolism, Lymphoma, T-Cell pathology, Neoplasm Proteins genetics, Nuclear Proteins genetics, PAX5 Transcription Factor, Transcription Factors genetics, Tumor Cells, Cultured, B-Lymphocyte Subsets metabolism, DNA-Binding Proteins biosynthesis, Gene Expression Regulation, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Lymphoma, B-Cell metabolism, Neoplasm Proteins biosynthesis, Neoplastic Stem Cells metabolism, Nuclear Proteins biosynthesis, Transcription Factors biosynthesis
- Abstract
The paired box containing gene PAX-5 encodes the transcription factor BSAP (B-cell-specific activator protein), which plays a key role in B-lymphocyte development. Despite its known involvement in a rare subtype of non-Hodgkin's lymphoma (NHL), a detailed examination of BSAP expression in NHL has not been previously reported. In this study, we analyzed normal and malignant lymphoid tissues and cell lines, including 102 cases of B-cell NHL, 23 cases of T- and null-cell NHL, and 18 cases of Hodgkin's disease. Normal lymphoid tissues showed strong nuclear BSAP expression in mantle zone B cells, less intense reactivity in follicular center B cells, and no expression in cells of the T-cell-rich zones. Monocytoid B cells showed weak expression, whereas plasma cells and extrafollicular large transformed B cells were negative. Of the 102 B-cell NHLs, 83 (81%) demonstrated BSAP expression. All of the 13 (100%) B-cell chronic lymphocytic leukemias (B-CLLs), 21 of (100%) mantle cells (MCLs), and 20 of 21 (95%) follicular lymphomas (FLs) were positive. Moderate staining intensities were found in most B-CLL and FL cases, whereas most MCLs showed strong reactions, paralleling the strong reactivity of nonmalignant mantle cells. Eight of 12 (67%) marginal zone lymphoma cases showed negative or low BSAP levels, and 17 of 24 (71%) large B-cell lymphomas displayed moderate to strong expression. None of the 23 T- and null-cell lymphomas reacted with the BSAP antisera, whereas in Hodgkin's disease, 2 of 4 (50%) nodular lymphocytic predominance and 5 of 14 (36%) classical cases showed weak nuclear or nucleolar BSAP reactions in a fraction of the tumor cells. Western blot analysis showed a 52-kD BSAP band in B-cell lines, but not in non-B-cell or plasma cell lines. We conclude that BSAP expression is largely restricted to lymphomas of B-cell lineage and that BSAP expression varies in B-cell subsets and subtypes of B-cell NHL. The high levels of BSAP, especially those found in large-cell lymphomas and in some follicular lymphomas, may be a consequence of deregulated gene expression and suggest a possible involvement of PAX-5 in certain B-cell malignancies. This is a US government work. There are no restrictions on its use.
- Published
- 1998
46. Cytotoxic granular protein expression, Epstein-Barr virus strain type, and latent membrane protein-1 oncogene deletions in nasal T-lymphocyte/natural killer cell lymphomas from Mexico.
- Author
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Elenitoba-Johnson KS, Zarate-Osorno A, Meneses A, Krenacs L, Kingma DW, Raffeld M, and Jaffe ES
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Immunohistochemistry, In Situ Hybridization, Killer Cells, Natural pathology, Lymphoma, T-Cell genetics, Lymphoma, T-Cell pathology, Lymphoma, T-Cell virology, Male, Mexico, Middle Aged, Nose Neoplasms genetics, Nose Neoplasms virology, Perforin, Poly(A)-Binding Proteins, Polymerase Chain Reaction, Pore Forming Cytotoxic Proteins, T-Cell Intracellular Antigen-1, Gene Deletion, Herpesvirus 4, Human genetics, Lymphoma, T-Cell metabolism, Membrane Glycoproteins metabolism, Membrane Proteins metabolism, Nose Neoplasms metabolism, Proteins, RNA-Binding Proteins metabolism, Viral Matrix Proteins genetics
- Abstract
Nasal T-lymphocyte/natural killer cell lymphomas (nT/NKLs) are a distinct group of neoplasms highly associated with Epstein-Barr virus (EBV), with a high prevalence in Asia but rare in Western countries. Recent studies indicate that these neoplasms are of cytotoxic T- or NK-cell derivation. Previous studies identifying a characteristic 30-base pair deletion within the 3' end of latent membrane protein-1 (del-LMP-1) in other EBV-associated lymphomas suggested a pathogenetic role for del-LMP-1 in those neoplasms. We examined 23 cases of nT/NKL from Mexico for expression of the cytolytic granular proteins TIA-1 and perforin (PRF), and for the presence of EBV by in situ hybridization (ISH). Polymerase chain reaction was performed to identify the EBV (EBNA-2) strain type and the status of the LMP-1 gene (del-LMP-1). Controls consisted of 11 sinonasal B-cell lymphomas (nBLs) and 30 reactive tonsils (RTs) from healthy Mexican individuals. The nT/NKLs expressed TIA-1 in 21 (91%) of 23 cases and PRF in 15 (65%) of 23 cases. In contrast, all of the nBLs were negative for TIA-1 and PRF. Twenty-two (96%) of 23 nT/NKLs were positive for EBV by ISH. In contrast, only 2 (18%) of 11 nBLs were positive for EBV by ISH. EBV strain Type A was identified in 21 (91%) of 23 cases, whereas strain Type B was present in 2 (9%) of the 23 nT/NKLs. A similar percentage (80%) of Type A was noted in 12 of the 15 RTs. del-LMP-1 was detected in 6 (26%) of 23 nT/NKLs, comprising 4 cases of Type A and 2 of Type B. del-LMP-1 was detected in 9 (45%) of 20 RTs. Our results indicated that TIA-1 and PRF were sensitive markers of nT/NKL. The presence of del-LMP-1 in comparable frequencies in the RTs and nT/NKLs suggested to us that this genotype was common in the Mexican population and argued against a definite pathogenetic role for del-LMP-1 in nT/NKL.
- Published
- 1998
47. Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes.
- Author
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Kumar S, Krenacs L, Medeiros J, Elenitoba-Johnson KS, Greiner TC, Sorbara L, Kingma DW, Raffeld M, and Jaffe ES
- Subjects
- Adult, Antigens, CD analysis, Apoptosis, DNA, Neoplasm analysis, Female, Granulocyte Colony-Stimulating Factor analysis, Herpesvirus 4, Human isolation & purification, Humans, Immunohistochemistry, Immunophenotyping, In Situ Hybridization, Infant, Lymphoma, T-Cell, Cutaneous chemistry, Male, Membrane Glycoproteins analysis, Membrane Proteins analysis, Middle Aged, Perforin, Poly(A)-Binding Proteins, Polymerase Chain Reaction, Pore Forming Cytotoxic Proteins, RNA-Binding Proteins analysis, Receptors, Antigen, T-Cell genetics, Skin Neoplasms chemistry, T-Cell Intracellular Antigen-1, T-Lymphocytes, Cytotoxic chemistry, Lymphoma, T-Cell, Cutaneous pathology, Panniculitis immunology, Panniculitis pathology, Proteins, Skin Neoplasms immunology, Skin Neoplasms pathology, T-Lymphocytes, Cytotoxic pathology
- Abstract
Subcutaneous panniculitic T cell lymphoma (SCPTCL) is characterized by primary involvement of the subcutaneous fat in a manner mimicking panniculitis. We studied 16 cases of this lymphoma to define its immunophenotypical profile as well as cellular origin. Involvement of the subcutaneous fat in a lacelike pattern with neoplastic cells rimming individual fat spaces was present in all cases. All 16 cases were of T cell phenotype. Thirteen of the 16 cases were CD8+, whereas three were negative for both CD4 and CD8. Twelve cases were stained for betaF1; of these, eight were betaF1+ and four were betaF1-. Focal staining for CD56 and CD30 was seen in 2 of 13 and two of eight cases, respectively. Intense diffuse positivity for the cytotoxic granular proteins T cell intracellular antigen-1 (TIA-1) and perforin was present in all cases, indicating an origin from cytotoxic T lymphocytes. Ten cases studied for Epstein-Barr viral sequences were negative. Eight of 9 cases with amplifiable DNA showed a clonal TCR gamma gene rearrangement by polymerase chain reaction. Controls included seven cases of benign panniculitis and seven other peripheral T cell lymphomas involving the skin and subcutaneous tissues: two peripheral T cell lymphomas, not otherwise specified (PTL,NOS), four anaplastic large cell lymphomas (ALCL), one T/NK cell lymphoma. The seven cases of panniculitis lacked cytological atypia and were characterized by an admixture of CD4+ and CD8+ cells with interspersed aggregates of L26+ B cells. Only infrequent cells showed staining for TIA-1 and perforin. In the control cases of T cell lymphoma, the infiltrate had a tendency for dermal and sometimes even epidermal involvement, with sheeting out of malignant cells, in contrast to the characteristic subcutaneous localization and rimming of fat spaces noted in SCPTCL. The two PTL, NOS were CD4+ and negative for both TIA-1 and perforin. Although the remaining controls expressed TIA-1 and perforin, in keeping with their cytotoxic T or natural killer (NK) cell origin, histological and other immunophenotypical features allowed distinction from SCPTCL. Five cases of SCPTCL were also stained for apoptosis using a tdt-mediated end labeling kit. All cases showed numerous positive apoptotic bodies, suggesting apoptosis as the mechanism of cell death in these tumors. Our study indicates that SCPTCL constitutes a distinctive clinicopathological entity derived from cytotoxic T lymphocytes and should be differentiated from other benign and malignant lymphoid infiltrates involving the subcutis. The apoptosis seen in these tumors may be mediated by release of cytotoxic granular proteins.
- Published
- 1998
- Full Text
- View/download PDF
48. Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T- and null-cell type and Hodgkin's disease: evidence for distinct cellular origin.
- Author
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Krenacs L, Wellmann A, Sorbara L, Himmelmann AW, Bagdi E, Jaffe ES, and Raffeld M
- Subjects
- Adolescent, Adult, CD4 Antigens analysis, CD56 Antigen analysis, CD57 Antigens analysis, CD8 Antigens analysis, Child, Child, Preschool, Female, Hodgkin Disease pathology, Humans, Infant, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Lymphoma, B-Cell immunology, Lymphoma, B-Cell pathology, Lymphoma, Large-Cell, Anaplastic pathology, Male, Membrane Glycoproteins biosynthesis, Membrane Glycoproteins immunology, Membrane Proteins biosynthesis, Membrane Proteins immunology, Middle Aged, Perforin, Poly(A)-Binding Proteins, Pore Forming Cytotoxic Proteins, RNA-Binding Proteins biosynthesis, RNA-Binding Proteins immunology, T-Cell Intracellular Antigen-1, T-Lymphocytes, Cytotoxic metabolism, Hodgkin Disease immunology, Lymphoma, Large-Cell, Anaplastic immunology, Proteins, T-Lymphocytes, Cytotoxic immunology
- Abstract
Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre, cells of T- or null-cell phenotype that show a preferential sinusoidal growth pattern and consistent CD30 positivity. Whether these tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule component, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further investigate this possibility, we performed an immunohistochemical study of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/ or CD30 positivity. We found that 76% of ALCLs, representing all subtypes except the PC forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1 and perforin were highly correlated (P < .001). On the basis of their immunophenotypic profiles, several subtypes of cytotoxic antigen positive and negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33) displayed an immunophenotypic profile consistent with cytotoxic T cells. Six cases expressed cytotoxic granular proteins in the absence of lineage specific markers, and one case expressed both T-cell- and natural killer cell-like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxic granule protein negative. All but one of these displayed a T-cell phenotype. Cytotoxic granule protein expression did not correlate with the presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found to be TIA-1+, and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic granule proteins in the majority of ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases originate from lymphocytes with cytotoxic potential. Furthermore, the demonstration of cytotoxic cell related proteins may be a useful addition to the current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL.
- Published
- 1997
49. bc1-1 rearrangement and cyclin D1 protein expression in multiple lymphomatous polyposis.
- Author
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Kumar S, Krenacs L, Otsuki T, Kumar D, Harris CA, Wellmann A, Jaffe ES, and Raffeld M
- Subjects
- Adult, Aged, Aged, 80 and over, Base Sequence, Cyclin D1, Female, Humans, Immunohistochemistry, Intestinal Polyps pathology, Lymphoma, B-Cell, Marginal Zone pathology, Lymphoma, Non-Hodgkin pathology, Male, Middle Aged, Molecular Sequence Data, Cyclins genetics, Gene Rearrangement, B-Lymphocyte, Intestinal Polyps genetics, Lymphoma, B-Cell, Marginal Zone genetics, Lymphoma, Non-Hodgkin genetics, Oncogene Proteins genetics, Proto-Oncogenes
- Abstract
Multiple lymphomatous polyposis (MLP), characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract, is believed to represent GI involvement by mantle cell lymphoma (MCL), primarily based on its histologic and immunophenotypic similarities with MCL. However, rearrangement of the bcl-1 locus, the molecular lesion characteristic of MCL, has not been investigated in this group of patients. The authors evaluated the morphologic, immunophenotypic, and molecular features of 18 cases of MLP and 8 B-cell lymphomas involving the GI tract (including 6 MALT lymphomas). All MLP cases presented with GI disease, and were histologically similar to MCL. DNA extracted from formalin-fixed, paraffin-embedded tissue was analyzed for evidence of bcl-1 rearrangement by PCR, using chromosome 11 specific and consensus JH primers. Amplifiable DNA was obtained in 24 of 26 cases (16 of 18 MLP cases and 8 of 8 controls). bcl-1 rearrangement was detected in 6 of 16 cases (38%), subsequently confirmed by sequencing of the breakpoint region, and in 0 of 8 controls. Immunostaining for cyclin D1 was positive in 14 of 18 MLPs, including the 6 bcl-1 rearranged cases and negative in 6 of 6 evaluable controls. The detection of bcl-1 rearrangement and cyclin D1 expression in cases of MLP supports the view that MLP represents primary MCL, of the GI tract. These techniques may also be helpful in differentiating MLP from other GI lymphomas, particularly low grade lymphomas of MALT, when only small routinely fixed endoscopic biopsies are available.
- Published
- 1996
- Full Text
- View/download PDF
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