Orientador: Irani Quagio-Grassiotto / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T21:20:24Z (GMT). No. of bitstreams: 1 Mazzoni_TalitaSarah_D.pdf: 26204829 bytes, checksum: b3ecbe44f1a0367d6194fb7c297136c2 (MD5) Previous issue date: 2013 / Resumo: Considerando o status atual de conhecimento da morfogênese e diferenciação gonadal nos Teleostei frente à restrição de informações, especialmente em aspectos tangentes ao estabelecimento do epitélio germinativo e sua relação com a formação da estrutura gonadal tomou-se aqui como modelos biológicos Tanichthys albonubes, Gymnocorymbus ternetzi, Corydoras schwartzi, Amatitlania nigrofasciata e Poecilia reticulata, representando as séries Otophysi, Percomorpha e Atherinomorpha, visando estabelecer uma análise comparativa da diferenciação gonadal entre as espécies, considerando suas posições na escala filogenética. A proliferação e diferenciação de células germinativas e somáticas a partir do primórdio gonadal em T. albonubes, G. ternetzi, C. schwartzi, A. nigrofasciata e P. reticulata levam à formação das diferentes estruturas ovarianas e testiculares e à constituição do epitélio germinativo que margeia as lamelas ovígeras e os túbulos/lóbulos testiculares. Nesses animais, o primórdio gonadal é formado por células germinativas primordiais (CGPs) rodeadas por células somáticas. Após sucessivas divisões mitóticas das células somáticas, o tecido gonadal aumenta, originando uma gônada indiferenciada, com as mesmas características morfológicas entre machos e fêmeas de T. albonubes e C. schwartzi. Em A. nigrofasciata e P. reticulata grupos de células germinativas e somáticas organizam-se de maneira distintas em machos e fêmeas. Nas gônadas femininas, as CGPs estão distribuídas por todo o tecido gonadal, enquanto que nas masculinas, as CGPs localizam-se na periferia. Na região dorsal das gônadas masculinas de A. nigrofasciata e P. reticulata, células somáticas organizam-se formando o ducto testicular, enquanto que em T. albonubes, G. ternetzi e C. schwartzi esse é a última estrutura a se formar. Nas gônadas femininas das cinco espécies, os processos envolvidos na diferenciação gonadal, como a foliculogênese, o estabelecimento do epitélio germinativo e a formação da cavidade ovariana são bastante semelhantes. Nas gônadas masculinas, as células somáticas, pré-Sertoli, associam-se às CGPs, formando cistos de espermatogônias; estas proliferam formando conjuntos celulares. Em T. albonubes e A. nigrofasciata os cistos de espermatogônias que constituem um mesmo conjunto, afastam-se uns dos outros, criando um espaço central, que se torna maior, originando um compartimento luminal, delimitado por cistos de espermatogônias. Formam-se os túbulos e lóbulos testiculares e o epitélio 2 germinativo masculino é estabelecido. Em G. ternetzi o tecido gonadal masculino é estabelecido e organizado em túbulos após a diferenciação gonadal feminina, sobre um ovário previamente desenvolvido, constituindo uma diferenciação gonocorística do tipo indireta. C. schwartzi apresenta um tecido gonadal masculino compacto, que sofre degenerações no interior de estruturas acinares compostas por cistos, para constituir os túbulos testiculares. Em P. reticulata, os conjuntos de espermatogônias conectam-se ao ducto em formação, originando os primeiros lóbulos testiculares. Ao final da diferenciação gonadal, os testículos de T. albonubes, G. ternetzi e C. schwartzi apresentam espermatogônias distribuídas aleatoriamente no túbulo. Estes anastomosam-se, caracterizando o testículo como tubular anastomosado. Em P. reticulata, as espermatogônias ficam restritas na região periférica dos lóbulos, os quais não apresentam lúmen testicular, características estas de um testículo lobular restrito. A mesma distribuição aleatória de cistos nos túbulos dos Otophysi ocorre nos lóbulos testiculares de A. nigrofasciata, caracterizando um testículo com organização lobular do tipo irrestrita / Abstract: Considering the lack of information about the gonadal morphogenesis and differentiation in Teleostei, especially in tangent aspects concerning the establishment of the germinal epithelium and its relation with the formation of the gonadal structure, in the present study, it was taken Tanichthys albonubes, Gymnocorymbus ternetzi, Corydoras schwartzi, Amatitlania nigrofasciata and Poecilia reticulata as biological models, representing the series Otophysi, Percomorpha and Atherinomorpha, to establish a comparative analysis of the gonadal differentiation among the species, taking into account their position in the phylogenetic scale. The proliferation and differentiation of germ and somatic cells from the gonadal primordium of the T. albonubes, G. ternetzi, C. schwartzi, A. nigrofasciata and P. reticulata lead to the formation of different testicular and ovarian structures and to the formation of the germinal epithelium of the ovigerous lamellae and the testicular lobules/tubules. In these animals, the gonadal primordium is formed by primordial germ cells (PGCs) surrounded by somatic cell. After successive mitotic divisions of the somatic cells, the gonadal tissue increases, resulting in a undifferentiated gonad, with the same morphological characteristics between males and females of T. albonubes and C. schwartzi. In A. nigrofasciata and P. reticulata groups of germ and somatic cells organize distinctly in males and females. In the female gonads, the PGCs are distributed throughout the gonadal tissue. In the male, the PGCs are located in the periphery. In the dorsal region of the male gonads of A. nigrofasciata and P. reticulata somatic cells are organized forming the testicular duct, whereas at T. albonubes, G. ternetzi and C. schwartzi this is the last structure formed. In female gonads of the five species, the processes involved in gonadal differentiation, such as folliculogenesis, the establishment of the germinal epithelium and the formation of the ovarian cavity are quite similar. In male gonads, the somatic cells, pre-Sertoli, associate to the PGCs forming cysts of spermatogonia; these proliferate and form clusters. In T. albonubes and A. Nigrofasciata, the cysts of the spermatogonia, which form a single cluster, move away from each other, creating a central space, which becomes greater, originating a luminal compartment, delimited by cysts of spermatogonia. Thus, testicular tubules and lobules are formed and male germinal epithelium is established. In G. Ternetzi, the male gonadal tissue is established and organized in tubules after the female gonadal 4 differentiation on an ovary previously developed, constituting an indirect gonochoristic differentiation. C. schwartzi presents a compact male gonadal tissue, which undergoes degeneration within acinar structures composed of cysts, forming the testicular tubules. In P. reticulata, the clusters of spermatogonia connect to the duct in formation, originating the first testicular lobules. At the end of gonadal differentiation, the testis from T. albonubes, G. ternetzi and C. schwartzi present spermatogonia, distributed along the tubule. These anastomose, characterizing the testis as anastomosing tubular. In P. reticulata, the spermatogonia are restricted at the periphery of the lobules, which do not have lumen, features of a restricted lobular testis. The same random distribution of cysts in the tubules of the Otophysi occurs in testicular lobules of A. nigrofasciata, featuring a testis with unrestricted lobular organization / Doutorado / Biologia Celular / Doutora em Biologia Celular e Estrutural

Cette thèse étudie Germinal et Au Bonheur des dames d'Émile Zola sous l'angle de l'histoire économique, de l'économie industrielle et du marketing. Elle cherche à déterminer ce que ces deux romans nous apprennent sur le fonctionnement des entreprises de la seconde moitié du XIXe siècle, et comment ils préfigurent l'actualité économique de la fin du XXe et celle du début du XXIe siècle. Les entreprises fictives de Zola sont non seulement représentatives des firmes réelles de l'époque, mais de plus elles rappellent certaines caractéristiques et stratégies de nos entreprises contemporaines. Par ses talents, l'extrême précision de sa méthode de recherche, son approche résolument différente de celle d'un historien de l'économie et son étonnante modernité en ce début du XXIe siècle, Zola rend la lecture de ces deux œuvres essentielle aux historiens de l'économie et aux économistes. La comparaison détaillée entre les entreprises fictives de ces romans et les réalités de l'industrie houillère et du commerce de détail de cette époque témoigne de leur véracité historique. Cette étude vise aussi à établir un parallèle entre les entreprises fictives de Zola et celles d'aujourd'hui en s'appuyant sur leurs caractéristiques et pratiques respectives en termes d'économie industrielle et de marketing. Enfin, cette thèse tente de discerner ce qui, dans le discours de beaucoup d'économistes contemporains sous-entend que l'origine des faits et pratiques économiques étudiés ici ne date que de quelques décennies. / This dissertation studies Émile Zola's Germinal and Au Bonheur des dames from the perspective of economic history, industrial economics and marketing. Its goal is to determine what these novels disclose on how companies functioned in the second half of the 19th century, and to which extent they anticipate the economic reality of the late 20th and early 21st centuries. Zola's fictional companies are not only representative of the real companies of that era but they also reflect some characteristics and strategies of the real firms of the early 21st century. Zola's talents, his meticulous method of research, his technique of economic analysis which significantly differs from that of an economic historian, and his ongoing modernity today make these novels a must for economic historians and economists alike. The detailed comparison between the fictional companies in the two novels and the real conditions in the mining and the retail industries ! vouch for their historical credibility. This study also aims at drawing a parallel between Zola's fictional companies and today's firms by analyzing their respective characteristics and practices in terms of industrial economics and marketing. Furthermore, this dissertation attempts to understand why many contemporary economists seem to suggest that the origin of the economic facts and practices studied here date back a couple of decades only.

The Early Growth Response genes 2 and 3 (Egr2/3) are zinc finger transcription factors that play an important role in the immune system. These transcription factors have reported functions in T cell receptor signaling, differentiation of effector T cell subsets and the development of lupus-like autoimmune diseases. Using CD2-Egr2-/- Egr3-/- mouse model, I investigate the development of inflammation pathology, differentiation of T follicular helper (Tfh) cells and the formation of germinal centers (GC) following viral challenge within these mice. The onset of inflammation pathology in CD2-Egr2-/- Egr3-/- mice was discovered to correlate with high levels of pro-inflammatory cytokines in the serum and the development of autoimmune diseases as previously reported by Li et al, 2012. Most importantly, a novel role for the Egr2/3 genes in the differentiation of T follicular helper (Tfh) cells was identified. Tfh cells are responsible for T cell dependent antibody immune response in the GC. They support the differentiation of GC B cells into plasma cells producing long lived high-affinity isotype-switched antibodies and memory B cells. Tfh cell differentiation is regulated by Bcl6 however; the regulators of Bcl6 during Tfh differentiation remain largely unknown. We have now discovered that Egr2/3 genes are required for Bcl6 expression during Tfh cell differentiation. In the absence of the Egr2 and 3 genes, Tfh cell differentiation is severely impaired and GC formation and functions were defective in response to Vaccinia Virus Western Reserve strain (VVWR) infection. Further investigation revealed that Egr2 regulated Bcl6 expression in a Tfh-specific manner as adoptive transfer of WT CD4+ T cells into Egr2-/- Egr3-/- mice was able to rescue Bcl6 expression, Tfh differentiation and GC formation. When the molecular mechanism of how Egr2 regulated Bcl6 was investigated, it was uncovered that Egr2 directly bound to the promoter region of Bcl6 gene in CD4 T cells to regulated Bcl6 expression. Indeed constitutive expression of either Egr2 or Bcl6 in CD2-Egr2-/- Egr3-/- CD4+ T cells rescued Tfh cell differentiation and GC formation. Our results inferred that the Egr2/3 genes are essential for Tfh differentiation and GC formation by regulating Bcl6 expression in CD4 T cells under Tfh condition. Our studies thus suggest that the Egr2/3 genes are paramount for minimising immunopathology and are also critical for efficient antibody production by regulating Tfh cell differentiation.

T follicular helper cells (T-FH) are a specialized subset of CD4 T cells that reside in B cell follicles and promote B cell maturation into plasma cells and long-lived memory B cells. During chronic infection prior to the development of AIDS, HIV-1 (HIV) replication is largely concentrated in T-FH. Paradoxically, T-FH numbers are increased in early and midstages of disease, thereby promoting HIV replication and disease progression. Despite increased T-FH numbers, numerous defects in humoral immunity are detected in HIV-infected individuals, including dysregulation of B cell maturation, impaired somatic hypermutation, and low quality of antibody production despite hypergammaglobulinemia. Clinically, these defects are manifested by increased vulnerability to bacterial infections and impaired vaccine responses, neither of which is fully reversed by antiretroviral therapy (ART). Deficits in T-FH function, including reduced HIV-specific IL-21 production and low levels of co-stimulatory receptor expression, have been linked to these immune impairments. Impairments in T-FH likely contribute as well to the ability of HIV to persist and evade humoral immunity, particularly the inability to develop broadly neutralizing antibodies. In addition to direct infection of T-FH, other mechanisms that have been linked to T-FH deficits in HIV infection include upregulation of PD-L1 on germinal center B cells and augmented follicular regulatory T cell responses. Challenges to development of strategies to enhance T-FH function in HIV infection include lack of an established phenotype for memory T-FH as well as limited understanding of the relationship between peripheral T-FH and lymphoid tissue T-FH. Interventions to augment T-FH function in HIV-infected individuals could enhance immune reconstitution during ART and potentially augment cure strategies.

Orientador: César Roberto Esper / Banca: marcelo Emilio Beletti / Banca: Pietro Sampaio Baruselli / Banca: Vera Fernanda Martins Hossepian de Lima / Banca: Humberto Tonhati / Resumo: Este estudo teve como objetivo acompanhar o processo de desenvolvimento testicular desde a fase indiferenciada até sua completa formação. Embriões e fetos de vacas da raça Nelore (Bos taurus indicus) foram obtidos em frigoríficos. Imediatamente após o abate das fêmeas, o útero era aberto e os embriões e fetos coletados. As gônadas e os embriões menores foram fixados em Bouin e processados para microscópica óptica convencional. Foi realizada a PCR (Reação em Cadeia da Polimerase) dos embriões cujo sexo não pode ser identificado macroscopicamente. A crista gonádica foi observada, primeiramente, em um embrião de 1,0 cm de comprimento. Em embriões com 2,5 cm de comprimento, a presença da albugínea permitiu a identificação do sexo. A espessura média da albugínea variou de 29,1 a 558,5 mm. O mediastino encontra-se localizado centralmente. Houve uma diminuição no espaço ocupado pelos cordões testiculares de 63,7 para 42,0% do volume total dos testículos. O seu diâmetro variou de 31,7 a 48,8 mm. O diâmetro das células germinativas (e dos seus núcleos) foi de 12,3 (6,6) a 16,9 (14,2) mm. A quantidade de células germinativas, por corte transversal de cordão, diminuiu de um máximo de 2,8 para 0,8. O número total de células germinativas aumentou de 16, no princípio da colonização da gônada, para 18,3 x 106 no final do estudo. O número de células de Sertoli, por corte transversal de cordão, variou de 10,0 a 16,2. Os resultados obtidos mostram que a origem e a formação dos testículos nos embriões e fetos de vacas da raça Nelore (Bos taurus indicus), ocorrem de forma muito semelhante à descrita para Bos taurus taurus. / Abstract: The aim of this study was to accompany the process of testicular development from the indifferentiable phase to its complete formation. Embryos and fetuses of Nelore breed cows (Bos taurus indicus) were obtained in slaughterhouses near the Uberlandia city, Minas Gerais. As soon as the females were slaughtered, the uterus was opened and the embryos and fetuses gathered. The gonads and the smaller embryos were fixed in Bouin's fixative and afterwards processed for conventional optical microscopy. It was carried out the PCR (Polymerase Chain Reaction) from parts of embryos whose sex could not be identified macroscopically. The gonadal ridge was observed firstly in a 1.0 cm long embryo. In 2.5 cm long embryos the presence of the albuginea allowed the sex identification. The mean thickness of the albuginea ranged from 29.1 to 558.5 mm. Gradually increase of vascularization of the albuginea and parenchyma was observed. The mediastinum was located centrally. There was a decrease in the space occupied by the testicular cords, from 63.7 to 42.0 % of the total testes volume. Its diameter ranged from 31.7 to 48.8 mm. The diameter of germinal cells (and their nuclei) ranged from 12.3 (6.6) to 16.9 914.2) mm. The quantity of germinal cells by cross section of cord decreased from a maximum of 2.8 to 0.86. The total number of germinal cells was from 16 at the beginning of colonization of the gonad to 18.3 x 106 at the end of the study. The number of Sertoli's cells by cross section of cord ranged from 10.0 to 16.2. The results showed that the origin and formation of testes in embryos and fetuses from Nelore breed cows (Bos taurus indicus) does occur in a very similar way to what is described for Bos taurus taurus. / Doutor

The germinal centre (GC) response is critical for generating highly effective humoral immune responses and immunological memory that forms the basis of successful immunisation. Control of the output of the GC response requires Follicular regulatory T (Tfr) cells, a subset of Foxp3+ Treg cells located within germinal centres. Tfr cells were first characterised in detail in 2011 and because of this relatively little is known about the exact role of Tfr cells within the GC, and the mechanism/s through which they exert their suppressive function. At the outset of this work, the major barrier to understanding Tfr cell biology was the lack of appropriate tools to study Tfr cells specifically, without affecting Tfh cells or other Treg cell subsets. This thesis set out to develop a strain of mice that specifically lacks Tfr cells. A unique feature of Tfr cells is their CXCR5-dependent localisation within the GC. Therefore, genetic strategies that exclude Treg cells from entering the GC are a rational approach to generating a mouse model that lacks Tfr cells. To this end, I generated a strain of mice that lacks CXCR5 on Foxp3+ Treg cells. These animals show a ~50% reduction in GC localised Tfr cells, and a GC response that is comparable to control animals. These data indicated that redundant mechanisms are involved in Treg cell homing to the GC. I identified CXCR4 as a chemokine receptor that is also highly expressed on Tfr cells, and hypothesised that it may also be involved in Tfr cell localisation to the GC. Surprisingly, simultaneous deletion of both CXCR4 and CXCR5 in Treg cells resulted in a less marked reduction in Tfr cells compared to deletion of CXCR5 alone, suggesting that CXCR4 might be involved in negative regulation of Treg homing to the GC. These data identify both CXCR4 and CXCR5 as key regulators of Tfr cell biology. Bcl6 drives Tfr cell differentiation, but how this transcriptional repressor facilitates commitment to the Tfr cell subset is unknown. I hypothesised that Bcl6 drives Tfr cell differentiation by repressing Tbx21, the transcriptional regulator involved in the differentiation of Th1-like Treg cells. I tested this hypothesis in Bcl6fl/fl CD4cre/+ animals and unexpectedly found that loss of Bcl6 regulates Treg cell differentiation in the absence of immunisation or infection. I have demonstrated that thymic loss of Bcl6 results in an increase in activated effector Treg cells, which occurs very early in life. These data point to a novel role for Bcl6 in preventing early thymic Treg activation, indicating that Bcl6 has a global role in Treg development and differentiation that is not simply limited to Tfr cells.

Haemorrhage within the germinal matrix with extension into the ventricle is commonly seen in very low birth weight babies. Outcome following severe haemorrhage, in particular when associated with post haemorrhagic hydrocephalus and congestive venous infarction is poor, whilst outcome following moderate degrees of haemorrhage remains variable. The Neural Stem Progenitor Cells (NSPC) within the GM have been shown to be exquisitely sensitive to micro-environmental cues, as such, haemorrhage within the GM is postulated to impact on neurological outcome through aberration of normal NSPC behaviour. Here we have developed a stereotactic model of autologous blood injection which recapitulates key features of Papile grade II/III Germinal Matrix Haemorrhage / Intraventricular Haemorrhage (GMH/IVH). This model demonstrates that GMH/IVH causes an activation of the NSPC within the wall of the lateral ventricle and increases the number of transient amplifying cells within the transcallosal pathway. Further to this RNA extraction from the NSPC (selected using a CD133 MACS protocol) revealed that GMH/IVH causes a significant down regulation of the transmembrane receptor Notch, a finding that was validated using Hes5 in situ hybridisation (ISH). Using a battery of behavioural tests including assessment of developmental landmarks, neuromotor and reflex development we found that GMH/IVH causes subtle but significant impacts on early neonatal development. GMH/IVH in transgenic mice overexpressing the polycomb group gene Bmi1 in NSC (Nestin+ve) revealed increased self-renewal and resistance to oxidative stress (properties of Bmi1 overexpression) reduced the impact of GMH on the oligodendrocyte population, it also revealed a unique behavioural phenotype. We propose that GMH/IVH down regulates Notch in the NSPC causing a burst of precocious proliferation and depleting the NSPC pool, which impacts on neurological outcome due to altered cortical architecture. Further we suggest that modulation of NSPC properties may play role in determining outcome and should be further explored for its therapeutic potential.

Made available in DSpace on 2016-04-25T20:21:36Z (GMT). No. of bitstreams: 1 ROGERIO HUMBERTO ZEFERINO NASCIMENTO.pdf: 1713697 bytes, checksum: 502ac3702d1eb8d2b448b789d223a9f1 (MD5) Previous issue date: 2006-05-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os estudos contemporâneos em torno das várias realizações dos anarquistas no Brasil, no período da Primeira República, estão, no geral, matizados por uma perspectiva disciplinar. Projetando sobre o movimento anarquista uma demanda que lhe é alheia, desconsideram aspectos significativos deste movimento. Os olhares disciplinados, estabelecidos no conjunto destas pesquisas, são cegos para apreender comportamentos e pensamentos refratários à disciplina. Ao contrário, aqui evidencio o caráter indisciplinar das iniciativas libertárias, focalizando-as como recusa tanto da hierarquia nas relações sociais como de um saber seccionado que outorga poder pastoral ao especialista. Poder este tão bem estudado por Foucault. A partir da análise de duas revistas e dois jornais anarquistas, publicados no eixo Rio-São Paulo entre os anos 1907 e 1915, sigo pistas que informam sobre a desoneração das linhas divisórias entre as áreas do conhecimento e, mais além, entre vida e saber. Não há como deixar de reconhecer aproximações com o nomadismo de Deleuze. Indisciplina como desrespeito às fronteiras; também como iconoclastia e antropofagia, concebendo a existência enquanto experimento. Por sua vez, produção e socialização de conhecimento acontecem numa vibração eminentemente coletiva. Neste processo, a noção de autodidatismo, como aporte conceitual explicativo, nada, ou quase nada, tem a dizer. As relações configuram vida e saber, devendo este, como afirma Max Stirner, morrer para se transformar em vontade, esta que é a força de oposição da pessoa. Stirner apresenta a educação disciplinar como adestramento, um constante cortar de asas, negando a singularidade do único. A indisciplina, para Stirner, é saudável!

Made available in DSpace on 2016-04-26T14:55:48Z (GMT). No. of bitstreams: 1 ROGERIO HUMBERTO ZEFERINO NASCIMENTO.pdf: 1713697 bytes, checksum: 502ac3702d1eb8d2b448b789d223a9f1 (MD5) Previous issue date: 2006-05-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os estudos contemporâneos em torno das várias realizações dos anarquistas no Brasil, no período da Primeira República, estão, no geral, matizados por uma perspectiva disciplinar. Projetando sobre o movimento anarquista uma demanda que lhe é alheia, desconsideram aspectos significativos deste movimento. Os olhares disciplinados, estabelecidos no conjunto destas pesquisas, são cegos para apreender comportamentos e pensamentos refratários à disciplina. Ao contrário, aqui evidencio o caráter indisciplinar das iniciativas libertárias, focalizando-as como recusa tanto da hierarquia nas relações sociais como de um saber seccionado que outorga poder pastoral ao especialista. Poder este tão bem estudado por Foucault. A partir da análise de duas revistas e dois jornais anarquistas, publicados no eixo Rio-São Paulo entre os anos 1907 e 1915, sigo pistas que informam sobre a desoneração das linhas divisórias entre as áreas do conhecimento e, mais além, entre vida e saber. Não há como deixar de reconhecer aproximações com o nomadismo de Deleuze. Indisciplina como desrespeito às fronteiras; também como iconoclastia e antropofagia, concebendo a existência enquanto experimento. Por sua vez, produção e socialização de conhecimento acontecem numa vibração eminentemente coletiva. Neste processo, a noção de autodidatismo, como aporte conceitual explicativo, nada, ou quase nada, tem a dizer. As relações configuram vida e saber, devendo este, como afirma Max Stirner, morrer para se transformar em vontade, esta que é a força de oposição da pessoa. Stirner apresenta a educação disciplinar como adestramento, um constante cortar de asas, negando a singularidade do único. A indisciplina, para Stirner, é saudável!

INTRODUÇÃO: Os linfomas B atualmente podem ser agrupados de acordo semelhanças moleculares e imunoistoquímicas com o linfócito do centro germinativo (CG) ou linfócito ativado (LA/pós CG), sendo este de pior prognóstico. O objetivo deste trabalho foi analisar a expressão de CD10, BCL-6 e MUM1 em pacientes portadores de LBPM e correlacionar com prognóstico. MÉTODOS: análise retrospectiva das variáveis clínicas e de tratamento de 44 pacientes portadores de LBPM. Estudo imunoistoquímico de CD10, BCL-6 e MUM1 em 29 pacientes com material disponível. RESULTADOS: idade mediana foi de 28 anos e 70% eram do sexo feminino. A positividade para CD10, BCL-6 e MUM1 foi de: 24%, 65% e 58%. De acordo com o modelo de Hans, 38% foi classificado como CG e 62% como pós CG. A sobrevida global em 5 anos e sobrevida livre de doença foi de 47% e 81%, respectivamente. Resposta Completa após quimioterapia de primeira linha (p=0,0001), radioterapia de mediastino (p=0,004) e IPI (0,039) tiveram associação com a sobrevida. A positividade para MUM1 esteve associado a pior sobrevida global (p=0,014). Aplicando o modelo de Hans não foi observada nenhuma associação com sobrevida. Na análise multivariada apenas Resposta (RR 4,28 (IC 95% 1,3-13,6) e MUM1 (RR 3,54 (1,1-11,5) correlacionaram com a sobrevida. CONCLUSÃO: Para este grupo de pacientes com características clínicas homogêneas, resposta completa e expressão de MUM1 estiveram associados à sobrevida. A classificação deste linfoma em CG e pós-CG utilizando CD10, BCL-6 e MUM1 não se correlacionou com evolução. Estudos futuros com casuística maior são necessários para melhor definir os fatores prognósticos do LBPM / INTRODUCTION: Primary Mediastinal Large B Cell Lymphoma (PMLBCL) is a distinct clinico-pathologic entity that differs from other Diffuse Large B Cell Lymphomas (DLBCL). Classification of DLBCL in GC and post-GC according can identify two subgroups of lymphomas with distinct prognosis. The aim of this study is to analyze the expression of CD10, BCL-6 and MUM1 in PMLBCL and correlate with prognosis. METHODS: retrospective analysis of clinical variables of 44 patients with PMLBCL and expression of CD10, BCL- 6 and MUM1 in 29 patients with available tissue. RESULTS: median age was 28 years and 70% of the patients were female. CD10, BCL-6 and MUM1 was positive in 24%, 65% and 58%, respectively. According to Hans classification, 38% were classified as GC and 62% as post-GC. Five year OS and DFS was 47% and 81%, respectively. In univariate analysis Complete Response (p=0.0001), Radiation therapy (p=0.004), IPI (0.039), and MUM1 expression (0.014) correlated with OS. No correlation was seen with Hans classification and survival. CONCLUSION: for this group of patients with homogeneous clinical features, response to therapy and MUM1 expression were associated with prognosis. The Hans algorithm proposed for aggressive lymphomas was not a predictive tool for survival in PMLBCL. Further studies are necessary to validate our finding and identify better prognostic variable for PMLBCL