PINTO, Marília Taumaturgo. Estudo comparativo da associação do vírus de epstein-barr com o linfoma de Hodgkin clássico em adulto : estudo imunohistoquimico e por hibridização in situ de casos do Ceará (Brasil) e de diferentes regiões da França. 2003. 80 f. Dissertação (Mestrado em Patologia) - Universidade Federal do Ceará. Faculdade de Medicina, 2003. / Submitted by denise santos (denise.santos@ufc.br) on 2011-12-22T13:48:11Z No. of bitstreams: 1 2003_dis_mtpinto.pdf: 641857 bytes, checksum: b7192fd1d4baa4ab6ad8b6e9c881c513 (MD5) / Approved for entry into archive by Eliene Nascimento(elienegvn@hotmail.com) on 2012-02-02T16:21:46Z (GMT) No. of bitstreams: 1 2003_dis_mtpinto.pdf: 641857 bytes, checksum: b7192fd1d4baa4ab6ad8b6e9c881c513 (MD5) / Made available in DSpace on 2012-02-02T16:21:46Z (GMT). No. of bitstreams: 1 2003_dis_mtpinto.pdf: 641857 bytes, checksum: b7192fd1d4baa4ab6ad8b6e9c881c513 (MD5) Previous issue date: 2003 / A associação do Linfoma de Hodgkin Clássico (LHc) com o vírus de Epstein-Barr (EBV) tem sido observada em vários países de diferentes condições sócio - econômicas. Recentemente usando-se técnica de Imunohistoquímica (IHQ) e Hibridização in situ (HIS) porções virais foi encontrada exclusivamente nas células características do Linfoma de Hodgkin que são as chamadas células de Reed-Sternberg (RS) e suas variantes chamadas células Hodgkin (H). Empregando estas técnicas nosso trabalho foi realizado de modo a fazer uma análise comparativa de uma amostra de 118 casos de origem do Ceará - Nordeste do Brasil e de diferentes regiões da França, sendo todos os pacientes de faixa etária entre 18 e 64 anos de idade. Com o propósito de convencionar parâmetros para análise comparativa e interpretação de resultados buscou-se alguns trabalhos de pesquisadores cujo objetivo maior era de avaliar o percentual dessa associação nos respectivos países onde observou- se uma escassez de trabalhos comparando dois ou mais países. A prevalência do EBV em lesões nodais de 37 pacientes do nordeste brasileiro com Linfoma de Hodgkin clássico foi comparada com 33 pacientes franceses.Houve predominância em pacientes brasileiros do sexo feminino (51,3%) e em pacientes franceses do sexo masculino (65,3%) sendo a média de idade similar em ambos os grupos (34,8 anos).Dos subtipos histológicos a Esclerose Nodular (EN) esteve presente em 23 casos brasileiros e em 29 franceses e Celularidade Mista (CM) em 11 brasileiros e 4 franceses. Depleção Linfocitária (DL) e não classificados foram raros. O LMP1 (Proteína de Membrana Latente) foi expresso nas células RS em 25 (67,5%) dos casos brasileiros e em 10 (30,3%) dos franceses e o Epstein-Barr encoded RNA (EBER) foi evidente em 75,6% de Brasil e 30,3% da França. A relação entre subtipo histológico e detecção viral foi mais freqüente no subtipo Celularidade Mista. Deduz-se com esses resultados que o EBV tenha uma maior participação na patogênese do LH Clássico nos casos do Ceará que em pacientes oriundos da França.

Orientador : Sara Teresinha Olalla Saad / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-02T22:15:41Z (GMT). No. of bitstreams: 1 Pagnano_KatiaBorgiaBarbosa_D.pdf: 5851139 bytes, checksum: e4d18bbf0ada55219fc1e87aaceeef3d (MD5) Previous issue date: 2002 / Resumo: Os linfomas não-Hodgkin (LNH) agressivos constituem um grupo heterogêneo de neoplasias hematológicas. Os LNH difusos de grandes células B compreendem cerca de 20-25% dos LNH. O tratamento quimioterápico pode curar apenas 40-50% dos pacientes adultos com linfomas agressivos. São considerados indicadores prognósticos: idade, número de sítios extranodais, LDH, performance status e estadiamento clínico. Além desses fatores, anormalidades das proteínas reguladoras do ciclo celular e da apoptose parecem ser um importante mecanismo de desenvolvimento de neoplasias e podem ter um papel no prognóstico dos linfomas agressivos. A expressão das proteínas reguladoras do ciclo celular, p53, p21/WAF-1, Mdm2 , c-Myc e PCNA (proliferating cell nuclear antigen) foram avaliadas através da análise imunohistoquímica de biópsias de gânglio, fixadas em formol e embebidas em parafina de 113 casos de LNH de alto grau de malignidade histológico, sendo que em 62 pacientes com LNH agressivos a expressão das proteínas foi correlacionada com dados clínicos e de sobrevida. Expressão de p53, p21/WAF-1, Mdm2 e c-Myc foi observada em 17/ 62 (30%), 25/60 (42%), 13/44 (30%) e 39/ 51 (76.5%) dos casos, respectivamente. O fenótipo p53+/p21WAF-1 negativo, que é mais freqüentemente encontrado nos casos com mutações do p53, foi associado com menor sobrevida global (SG), (P=0.04) e uma menor taxa de remissão completa (RC) (P=0.01). Expressão negativa de p53 e c-Myc foram relacionadas a uma melhor resposta à quimioterapia (P=0.005 e 0.035, respectivamente). A expressão de p53, c-Myc e Mdm2 foi associada a uma menor SG (P < 0.001, 0.05 e 0.037 respectivamente), sugerindo que a expressão dessas proteínas poderia estar associada a um pior prognóstico nesses pacientes. Além da análise da expressão da p53, pesquisamos a presença de mutações do gene p53 nos casos com hiperexpressão da proteína (n=17). Foi possível extrair DNA de 15 casos. A amplificação dos éxons 5-9 do p53 teve êxito em 7 casos, com o achado de uma mutação de ponto no éxon 6 (Val®Glu;T®A), num paciente com hiperexpressão da p53 e expressão negativada p21/WAF-1.Avaliamos também a expressão de proteínas reguladoras da apoptose (p53, Bcl-2, Bax, Bak e Mcl-1) de 33 pacientes com LNH difusos de grandes células B e analisamos a relação entre a expressão dessas proteínas com dados clínicos e resposta à quimioterapia. Nossos resultados mostraram que a expressão da p53 foi considerada um parâmetro imunohistoquímico independente relacionado a um pior prognóstico nesses linfomas. Apesar da alta expressão observada das proteínas Bcl-2, Bax, Bak e Mcl-1, não foi encontrado associação com prognóstico ou resposta ao tratamento / Abstract: Aggressive non-Hodgkin¿s lymphomas (NHL) form a heterogeneous group in terms of clinical presentation, histology, immunophenotype, response to treatment and prognosis. Diffuse large B-cell NHL (DLCL) constitute up to 20-25% of NHL in many series. Combination chemotherapy may cure 40-50% of adult patients. Several clinical prognostic factors have been described to predict clinical outcome, as age, LDH, performance status, and stage and are useful for identifying high-risk patients, who would benefit from a more intensive approach. Abnormalities of cell cycle and apoptosis regulating proteins seem to be an important mechanism of tumorigenesis and may play a role in the prognosis of aggressive NHL. The expression of p53, p21/WAF-1, Mdm2 , c-Myc and proliferating cell nuclear antigen (PCNA) proteins were examined by the immunohistochemistry of paraffin embedded tissues of 113 high grade non-Hodgkin's lymphomas (NHL) and in 62 patients with aggressive NHL correlated to clinical data. Expression of p53, p21/WAF-1, Mdm2 and c-Myc protein was observed in 17 out of 62 cases (30%), 25 out of 60 (42%), 13 out of 44 (30%) and 39 out of 51 (76.5%), respectively. The p53+/p21WAF-1 phenotype, which is more frequently found in p53 mutations, was associated with a worse overall survival (P=0.04) and with a lower rate of complete response (CR)(PF=0.01). p53 and c-Myc negative expression was related to a better response to chemotherapy (PF=0.005 and 0.035, respectively). The expression of p53, c-Myc and Mdm2 was related to a shortened overall survival (P < 0.001, 0.05 and 0.037 respectively), suggesting that the expression of these proteins could be associated with a poor outcome in these patients. We looked for mutations of p53 gene in aggressive NHL patients with hiperexpression of p53 protein (n=17). DNA extraction was performed in 15 patients and PCR amplification of exons 5-9 was possible in 7 cases. We found a point mutation in exon 6 (Val®Glu;T®A), in a patient with p53 hiperexpression and p21 negative expression. We also evaluated the expression of apoptosis-regulating proteins (p53, Bcl-2, Bax, Bak and Mcl-1) of paraffin-embedded tissues of 33 patients with diffuse large B-cell NHL, and assessed the relationship of these proteins to clinical outcome and response to chemotherapy. Our results showed that p53 expression was an independent immunohistochemical parameter related to a poor prognosis in these lymphomas. Bcl-2, Bax, Bak and Mcl-1 proteins, though highly expressed in almost all cases were not associated with prognosis or response to treatment / Doutorado / Doutor em Clínica Médica

Made available in DSpace on 2014-06-12T18:07:44Z (GMT). No. of bitstreams: 2 arquivo786_1.pdf: 1734258 bytes, checksum: 4c36030a28c129a7be1b991361c6a5d5 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2010 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O Linfoma de Hodgkin (LH) é uma neoplasia maligna caracterizada histologicamente pela presença de células denominadas Hodgkin-Reed-Sternberg (H-RS) no microambiente tumoral. A interleucina-10 (IL-10) é uma citocina imunoregulatória que exerce função linfoproliferativa nas células B. A regulação do produto do IL-10 pode ser controlado por diferentes genótipos no promotor do gene ou por transcritos do vírus Epstein-Barr (EBV) em células B infectadas, já que o EBV possui a capacidade de produzir uma IL-10 (vIL-10) similar a IL-10 humana (hIL-10). Os polimorfismos de base única (SNP) na posição proximal do promotor do gene IL-10 já foram relacionados com diversas doenças, entre elas o LH em algumas populações. Assim, o objetivo deste trabalho foi investigar a existência de associação entre os polimorfismos proximais do IL-10 com LH e a possível associação com EBV. O estudo foi do tipo analítico com caso-controle, consistindo de 64 pacientes (2-18 anos) com LH, atendidos no CEONPE/HUOC e 131 indivíduos saudáveis compondo o grupo de controles. A investigação dos SNPs nas posições - 1082 e -592, e de dos seus possíveis haplótipos, foi realizada por PCR alelo específica (AS-PCR). A análise do EBV foi realizada por hibridização in situ fluorescente da detecção do RNA do vírus Epstein-Barr (EBER-ISH). Indivíduos com genótipo -1082GG apresentaram 4,5 vezes menos chance de desenvolver LH que os portadores dos demais genótipos (OR = 4,45, IC95% 1,5-13,3 p = 0,007). Indivíduos com o genótipo -592CC apresentaram cerca de cinco vezes menos chance de desenvolver o LH que portadores dos demais genótipos (OR = 5,27, IC95% = 1,53- 18,1 p = 0,007). Em relação aos haplótipos, portadores do haplótipo ACC apresentaram três vezes mais chances de desenvolver LH, em comparação aos demais haplótipos (OR= 3,28 IC95% 1,18 9,07 p= 0,03). Indivíduos com os haplótipos combinados ATA/ATA e GCC/GCC apresentaram menos chances de desenvolvimento do LH, em comparação às demais combinações (OR= 0,19 IC 95% 0,05 0,65 p= 0,007 e OR= 0,225 IC 95% 0,07 0,66 p= 0,007). A presença do EBV foi verificada em 36,8% das amostras analisadas. A amostra de casos de EBV apresentou maior freqüência do haplótipo ACC nos indivíduos EBV +; Já nos indivíduos EBV-, o haplótipo ATA apresentou maior freqüência; Em conclusão, as variantes genéticas das posições -1082 e -592 e os haplótipos sugerem associação ao risco de desenvolvimento de LH nos indivíduos do grupo estudado; A associação com o EBV não pode ser inferida nesta análise

Orientador: Jose Vassalo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-14T01:57:16Z (GMT). No. of bitstreams: 1 Faria_SergioLuizCamposdeOliveira_D.pdf: 8719640 bytes, checksum: d89b1471ada863022607603778d80ad2 (MD5) Previous issue date: 1991 / Resumo: O presente trabalho faz uma revisão histopatológica, com várias correlações clinicas, de todos os pacientes com DH vistos de setembro/78 a outubro/88 no Centro Infantil de Investigações Hematológicas Dr. Domingos A. Boldrini (Centro Boldrini), Campinas-SP.Compara estes dados com uma abrangente revisão da literatura. Dos 46 casos vistos no periodo, 37 foram avaliados (9 foram excluidos em virtude de terem feito tratamentos em outros serviços). A idade mediana foi de 7 anos com predominânia do sexo masculino (2:1). Quase metade dos casos, 17/37 (46%), tiveram sintomas sistêmicos tipo "B" (nos paises desenvolvidos a presença de sintomas "B" é mais baixa e varia de 18% a 27%). Metade dos 37 casos foram estádios 111 e IV. Os tratamentos variaram pouco durante este periodo de 10 anos: radioterapia exclusiva (2 casos), esquemas de tratamentos combinados com radioterapia e quimioterapia (em geral MOPP). A partir do segundo semestre de 1986 o Centro Boldrini tratou, as crianças com DH pela orientação do, grupo alemão BFM que preconiza 2 ciclos de quimioterapia (QT) para estádios I e lIA; 4 ciclos de QT para IIB e IIIA e 6 ciclos de QT para IIIE e IV, todos seguidos de radioterapia em campos localizados ¿Observação: O resumo, na íntegra poderá ser visualizado no texto completo da tese digital. / Abstract: Hodgkin's Disease. (HD) in children is uncommon; represented only 0.08% of alI cancers in Brasil during 1976-80. It has been treated differently of the adult's HD because radiotherapy in children has been associated to frequent late complications. This work anaIysed alI patients seen in Centro de InvestigaçõesHematológicas Dr. Domingos A.Boldrini, in Campinas, Brazil, between September/78and October/88. AlI cases had their slides re-classified pathologically and results were compared with an extensive review of the literature. Nine of the 46 children with HD seen in that period were not considered in the study because they were not totally treated in Centro Boldrini. Among the 37 patients studied, median age was 7 years old with predominance of males (2:1). Forty six percent (17/37) had constitutional symptoms "E" (in developed countries this number is around 18%- 27%). Half of the patients were stage 111 and IV. Treatments changed during the period of study: from exclusive radiotherapy to combined modality with chemotherapy and radiation. Starting in July/86 alI children were conducted under the orientation of the German DAL MulticenterGroup (EFH) with 2 cycIes of chemotherapy (CT) for stages I and lIA; 4 cycles of CT for stages IIE and IIIA and 6 cycles of CT for stages IIIE and IV, always followed by radiotherapy in involved fields ...Note: The complete abstract is available with the full electronic digital thesis or dissertations. / Doutorado / Anatomia Patologica / Doutor em Ciências Médicas

Class of 2017 Abstract / This project is related to the article that was later published, available at this link: https://doi.org/10.1016/j.critrevonc.2016.11.009 / Objectives: Brentuximab vedotin (BV) is an antibody-drug conjugate comprising a CD30-directed antibody conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma and relapsed systemic Methods: primary study outcomes being objective response rate. PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015). Inclusion criteria included all studies and case reports of NHLs in which BV therapy was administered. Twenty-eight articles met these criteria. Results: Utilizing the twelve clinical subtypes, we found clinical evidence of BV and stratified the study populations into three groups: B-cell malignancies (group A), T-cell malignancies (group B), and non-B or non-T-cell hematological malignancies (group C). Across the group A malignancies, there were 87 patients. 48% experienced an objective response (OR). Across the group B malignancies, there were 274 patients. 74% experienced an OR. Across the group C malignancies, there were 9 patients. 44% experienced an OR. Conclusions: Our findings indicate that BV induces a variety of responses, largely positive and variable between NHL subtypes. With properly powered prospective studies, BV may prove to be a strong candidate in the treatment of CD30+ malignancies.

Cochlear implants (CIs) are prosthetic devices used to partially restore hearing for profound and severely deaf individuals. CIs convert sounds into electrical pulses which stimulate the auditory nerve fibers. An accurate model of auditory nerve fibers (ANFs) would help in improving the functionality of CIs. Previous studies have shown that the original Hodgkin-Huxley (1952) model (with kinetics adjusted for mammalian body temperature) may be better at describing nodes of Ranvier in ANFs than models for other mammalian axon types. However, the Hodgkin-Huxley model is still unable to explain a number of phenomena observed in auditory nerve responses to CI stimulation, such as short-term and long-term adaptation, the time-course of relative refractoriness, and stimulus-dependent random fluctuations in membrane threshold. Recent physiological investigations of spiral ganglion cells have shown the presence of a number of ion channel types not considered in the previous modelling studies, including low-threshold potassium (𝐼^KLT) channels and hyperpolarization-activated cation (𝐼^h) channels. In this thesis, inclusion of these ion channel types in a stochastic Hodgkin-Huxley model is investigated. Four versions of the model are formed and compared: that is, the standard Hodgkin-Huxley model, the standard model with /h only added, the standard model with 𝐼^KLT only added, and finally, the standard model with both h and 𝐼^KLT added. Two group of responses are explored: i) single-pulse responses and ii) pules-train responses. For the single pulse responses, a charge-balanced biphasic stimulus pulse is used. The effect of varying the pulse-width and the interphase gap is investigated for both leading phase polarities. Results are compared to responses for single monophasic stimulus pulses in some cases. Pulse-train responses are investigated for charge-balanced depolarizing-phase leading biphasic pulses at rates of 200, 800, and 2000 pulse/s. Results from single-pulse responses show an increase in spike threshold when one or both of these channel types are included. The addition of 𝐼^KLT increases random threshold fluctuations in the stochastic model, particularly for longer pulse widths. For pulse-train responses, rapid adaptation in spike rate may be resulting from 𝐼^KLT whereas 𝐼^h produces slower "short-term" adaptation. Thus, the simulation results suggest that including 𝐼^KLT and/or 𝐼^h in a Hodgkin-Huxley model improves the accuracy of the model in describing auditory nerve fiber responses during cochlear implant stimulation. / Thesis / Master of Applied Science (MASc)

No description available.

No description available.

Das follikuläre Lymphom ist eines der häufigsten Non-Hodgkin Lymphome und überwiegend eine Erkrankung des erwachsenen Menschen. In der WHO-Klassifikation ist es als ein Lymphom von Keimzentrumszellen definiert, das follikulär und/oder diffus wachsen kann. Zur Subklassifikation follikulärer Lymphome empfiehlt die WHO-Klassifikation eine Unterscheidung der Grade 1, 2 und 3 durch Auszählen der Zentroblasten pro zehn Gesichtsfelder in starker Vergrößerung. Beim Grad 3A liegen neben Zentroblasten auch Zentrozyten vor. FL Grad 3B bestehen ausschließlich aus Zentroblasten. Hinsichtlich der Zytomorphologie, Immunhistologie und Genetik bestehen deutliche Unterschiede zwischen FL Grad 1, 2 und 3A gegenüber FL Grad 3B. In der vorliegenden Arbeit konnte gezeigt werden, dass die weit überwiegende Zahl der follikulären Lymphome Grad 1, 2 und 3A ein prädominant follikuläres Wachstumsmuster aufwies. Ein follikulärer und diffuser Wuchstyp lag seltener vor. Noch seltener war ein überwiegend bzw. „rein“ diffuses Wachstumsmuster. Die mitotische und proliferative Aktivität stieg mit dem Tumorgrad linear an. Hinsichtlich der CD10 Reaktivität, der BCL-2 und p53 Expression sowie des Nachweises einer sekretorischen Differenzierung ergaben sich beim Vergleich der FL Grad 1 bis 3A keine statistisch signifikanten Unterschiede. Die BCL-2 Expression nahm allerdings bei den FL1-3A mit zunehmendem Grad ab. In zytogenetischen Untersuchungen wurden in allen follikulären Lymphomen Grad 1 bis 3A primäre bzw. sekundäre Chromosomenaberrationen gefunden. Unter den rekurrenten chromosomalen Alterationen trat die Translokation t(14;18)(q32;q21) am häufigsten auf und war insbesondere bei follikulären Lymphomen Grad 1 und 2, in etwas geringerem Maße auch bei FL Grad 3A anzutreffen. Diese Translokation scheint also in einem frühen Stadium der B-Zell-Entwicklung aufzutreten und führt primär zu einem höher differenzierten (zentrozytenreichen) Lymphom. Die t(14;18) bedingt zumeist eine Überexpression des BCL-2 Gens, die sich auch immunhistochemisch nachweisen lässt und diagnostische Verwendung findet. Das BCL-2 Protein ist daher von Nutzen für die Unterscheidung neoplastischer von reaktiven Follikeln, nicht aber, um follikuläre von anderen „low grade“ B-Zell Lymphomen zu unterscheiden. Die sekundären Alterationen charakterisieren bestimmte undifferenzierte Stadien mit hohem Blastenanteil und einer hohen mitotischen und proliferativen Aktivität. In zytogenetischen Untersuchungen von überwiegend diffus wachsenden FL konnte keine Translokation t(14;18)(q32;q21) nachgewiesen werden. Die identische Morphologie dieser Lymphome und die identischen Veränderungen auch auf genetischer Ebene deuten auf die nahe Verwandtschaft der überwiegend diffus wachsenden FL mit den typischen Keimzentrums-lymphomen hin. Es handelt sich jedoch um eine eigenständige Identität, die differenzierten Keimzentrumslymphome, die wahrscheinlich aufgrund des Fehlens einer t(14;18)(q32;q21) ein primär und ausgeprägt diffuses Wachstumsmuster aufweisen. / The follicular lymphoma is predominant one the most frequent Non Hodgkin of lymphomas and an illness of the adult humans. In the WHO classification it is defined as a lymphoma of germ center cells, which can grow follicular and/or vaguely. To the Subklassifikation of follicular lymphomas the WHO classification recommends a distinction of the degrees of 1, 2 and 3 by counting out the centroblasten per ten visual field in strong enlargement. With the degree of 3A also centrocyten are present beside centroblasten. Flat steel bars degrees of 3B exclusively consist of centroblasten. Regarding the cytomorphology, immunhistology and genetics clear differences between flat steel bar degrees 1, 2 and 3A exist opposite flat steel bar degree 3B. In the available work it could be shown that the number of the follicular lymphomas degrees of 1, 2 and 3A outweighing far predominant folliculars growth sample exhibited. A follicular and diffuse type of stature was present more rarely. Still more rarely a “diffuse growth sample was predominant and/or „pure. The mitotic and proliferative activity rose with the tumor degree linear. Regarding the CD10 reactivity, the BCL-2 and p53 Expression as well as the proof of a secretoric differentiation did not result in the case of the comparison of the flat steel bars degrees of 1 to 3A statistically significant differences. The BCL-2 Expression removed however with the FL1-3A with increasing degree. In cytogenetic investigations in all follicular lymphomas degrees of 1 to 3A primary and/or secondary chromosome aberrations were found. Under the recurrent chromosomalen old person rations the translokation t (14 stepped; 18) (q32; q21) most frequently up and was in particular with follicular lymphomas degree of 1 and 2 to find in somewhat smaller measure also with flat steel bar degree of 3A. This translokation seems to arise thus in an early stage of the B-cell-development and leads primarily to a more highly differentiated (centrocyt) lymphoma. The t (14; ) mostly a overexpression of the BCL-2 of gene, which can be proven also immune-histochemical, causes 18 and diagnostic use finds. The BCL-2 protein is from there of use for the distinction more neoplastic of reactive follicles, not however, in order to differentiated follicular from others „low degrees “B-cell lymphomas. The secondary old person rations characterize certain undifferentiated stages with high blowing portion and a high mitotic and proliferativen activity. In cytogenetic investigations of predominantly vaguely growing flat steel bar no Translokation t (14 could; 18) (q32; q21) to be proven. The identical morphology of these lymphomas and the identical changes also on genetic level point growing flat steel bar with the typical germ center lymphomas to the close relationship that predominantly vaguely. However the differentiated germ center lymphomas, those concern probably due to the absence of a t their own identity, (14; 18) (q32; q21) primarily and minted diffuse growth sample exhibit.

Obwohl sie die Mehrzahl der T-Zell-Lymphome darstellen, war über die Genetik der PTC-NOS und ALK-negativen ALCL bisher nur wenig bekannt. Klassische zytogenetische Untersuchungen dieser Gruppe wiesen auf komplexe chromosomale Veränderungen hin. Aufgrund der Seltenheit dieser Neoplasien basierten die Berichte bis jetzt nur auf einer geringen Anzahl von Fällen. Für die heterogene Gruppe von PTCL-NOS konnten bisher keine charakteristischen genetischen Veränderungen beschrieben werden. Zudem waren die genetische Beziehung zwischen ALK-negativen ALCL und PTCL-NOS, die Genetik von kutanen ALCL und die sekundären genetischen Veränderungen in ALK-positiven ALCL unklar. In dieser Untersuchung wurden 42 PTCL-NOS und 37 ALCL, davon 17 anaplastisch-großzellige Kinase (ALK)-negative ALCL, 9 ALK-positive ALCL und 11 kutane ALCL, durch komparative genomische Hybridisierung analysiert und charakteristische rekurrente genetische Alterationen nachgewiesen. Unter 36 primär diagnostizierten PTCL-NOS fanden sich rekurrente chromosomale Verluste auf den Chromosomen 13q (minimal überlappende Region 13q21, 36% der Fälle), 6q und 9p (6q21 und 9p21-pter, in 31% der Fälle), 10q und 12q (10q23-24 und 12q21-q22, in 28% der Fälle) und 5q (5q21, 25% der Fälle). Rekurrente Zugewinne wurden auf Chromosom 7q22-qter (31% der Fälle) gefunden. In 11 PTCL-NOS wurden High-level-Amplifikationen beobachtet. Bei den PTCL-NOS konnte zudem eine Gruppe von nicht-zytotoxischen nodalen CD5-positiven T-Zell-Lymphomen abgegrenzt werden, die durch rekurrente chromosomale Verluste auf den Chromosomen 5q, 12q und 10q charakterisiert ist. Während kutane und ALK-positive ALCL wenige rekurrente chromosomale Veränderungen zeigten, fielen bei ALK-negativen ALCL wiederholt Zugewinne auf Chromosom 1q (1q41-qter, 46%) und Verluste auf Chromosom 6q (6q21, 31%) und 13q (13q21-q22, 23%) auf. Insgesamt können somit PTCL-NOS von ALK-negativen ALCL durch Verluste auf den Chromosomen 5q und 9p (bei PTCL-NOS) sowie durch Zugewinne auf Chromosom 1q (bei ALCL) abgegrenzt werden. PTCL-NOS und ALK-negative ALCL unterscheiden sich genetisch außerdem von anderen T-NHL, wie Enteropathie-assozierte T-Zell-Lymphome, Prolymphozyten-Leukämien vom T-Zell-Typ und adulte T-Zell-Leukämien/Lymphomen. / Although representing the majority of T-cell lymphomas, the genetics of PTCL NOS and ALK-negative ALCL are only poorly characterized so far. Classical cytogenetic studies have demonstrated a high degree of chromosomal complexity. Because of the rarity of these neoplasms, most reports were based on a small number of cases only. For the heterogeneous group of PTCL NOS, no characteristic genetic alterations have been defined so far. In addition, the genetic relationship between ALK-negative ALCL and PTCL NOS, the genetics of cutaneous ALCL, and the secondary genetic alterations in ALK-positive ALCL have remained enigmatic so far. In this study 42 PTCL NOS and 37 ALCL [17 anaplastic large cell kinase (ALK)-negative ALCL, 9 ALK-positive ALCL, 11 cutaneous ALCL] were analyzed by comparative genomic hybridization. Among 36 de novo PTCL NOS, recurrent chromosomal losses were found on chromosomes 13q (minimally overlapping region 13q21, 36% of cases), 6q and 9p (6q21 and 9p21-pter, in 31% of cases each), 10q and 12q (10q23-24 and 12q21-q22, in 28% of cases each), and 5q (5q21, 25% of cases). Recurrent gains were found on chromosome 7q22-qter (31% of cases). In 11 PTCL NOS, high-level amplifications were observed. Whereas cutaneous ALCL and ALK-positive ALCL showed few recurrent chromosomal imbalances, ALK-negative ALCL displayed recurrent chromosomal gains of 1q (1q41-qter, 46%), and losses of 6q (6q21, 31%) and 13q (13q21-q22, 23%). Losses of chromosomes 5q, 10q, and 12q characterized a group of noncytotoxic nodal CD5+ peripheral T-cell lymphomas. Losses of chromosome 5q and 9p (PTCL) and gains of chromosome 1q (ALCL) may segregate PTCL NOS from ALK-negative ALCL. The genetics of PTCL NOS and ALK-negative ALCL differ from other T-NHLs characterized genetically so far, among them enteropathy-type T-cell lymphoma, T-cell prolymphocytic leukemia, and adult T-cell lymphoma/leukemia.