Les cyclines D jouent un rôle essentiel dans les mécanismes du cycle cellulaire. Cette famille de protéines est composée de trois membres (D1,D2,D3) qui partagent un domaine très homologue de la « cyclin box » (codée par les exons 1-3). Ce domaine est responsable de leur activité redondante dans la phosphorylation de la protéine du rétinoblastome lors de l'association avec les kinases cycline-dépendantes CDK4/6. Parmi les trois cyclines, la cycline Dl, bien que faiblement exprimée dans les lymphocytes, est la cycline la plus impliquée dans les cancers lymphoïdes ou elle aurait une fonction de facteur de transcription indépendante de Cdk. Etant donné qu'après stimulation antigénique, les lymphocytes T et B ont une capacité remarquable de division, essentielle à la génération d’une réponse immunitaire efficace, nous avons porté un intérêt particulier au rôle des cyclines D dans la lymphopoïèse. Pour étudier le rôle de la cycline Dl dans la différenciation des lymphocytes, nous avons utilisé des souris déficientes pour les exons 1,2,3 de la « cycline box » Dl mais conservé les exons 4 et 5. Étonnamment, ces souris présentaient des phénotypes très différents que nous avons subdivisés en quatre groupes. Dans le groupe I, les souris avaient un thymus réduit car la différenciation de la lignée lymphoide est bloquée à un stade très précoce, avec un faible nombre de cellules progénitrices (CLP) dans la moelle osseuse. Dans le thymus, les progéniteurs des thymocytes (ETP) étaient pratiquement absents et les précurseurs CD4CD8CD3 (TN) immatures essentiellement constitués par des cellules CD44*CD25 (TN1) et CD44*CD25+ (TN2) les plus immatures. De plus, les CD4*CD8* (DP) qui donnent naissance aux thymocytes matures CD4+ et CD8+ étaient présents en très faible quantité. Dans la moelle osseuse, on observe un blocage majeur dans la différenciation de la lignée B au stade pré-proB. Dans les ganglions, la forte réduction du nombre de lymphocytes T observée était liée au faible nombre d'ETP et à l’absence du récepteur aux chimiokines CCR7. Dans le groupe II, les souris présentaient une diminution moins sévère des ETP et une atrophie modérée du thymus. La différenciation était bloquée à un stade ultérieur, soit dans la transition des étapes TN3 à TN4. Dans la moelle osseuse, les lymphocytes B ont subi un blocage partiel au stade pré-proB et une réduction des cellules pré-B. Le nombre de CLP est également réduit, mais dans une moindre mesure que dans les souris du groupe I. dans les groupes III et IV, les souris ont une répartition normale des thymocytes mais présentaient une augmentation du compartiment ETP. Alors que les souris du groupe III contenaient un nombre normal de thymocytes, les souris du group IV présentaient une hyperplasie thymique. Par ailleurs, en comparaison avec des souris normales, bien que la différenciation des lymphocytes B soit normale, on observe dans les deux groupes une augmentation des CLP et des progéniteurs hématopoïétlque (LSK). L’implication de la cycline Dl dans la transition de G1 à S nous a conduit à analyser les divisions cellulaires in vivo. De manière surprenante, les souris du groupe I étaient fortement dépourvues de cellules en cycle dans tous les compartiments lymphoïdes, ce qui peut expliquer les blocages de la différenciation lymphoide. Par contre, dans les trois autres groupes, on observe une augmentation du nombre de divisions cellulaires. Ces résultats différents peuvent être dû à l'expression ou l'absence d'une protéine Dl tronquée qui contient cependant les exons 4-5. Alors que ces ARNm tronqués ne sont pas détectables dans les souris de groupe I, on observe des niveaux élevés d'expression dans les autres groupes. De plus, nous avons observé une corrélation entre l'absence d’expression des exons 4-5 et la très faible expression des gènes CCND2 et CCND3, ce qui attribue à cette protéine tronquée un rôle prépondérant dans la régulation des cyclines D et permet d’expliquer l'aplasie profonde et… / D Cyclins play an essential role connecting exogenous stimulation to the intrinsic cell cycle machinery. This family of proteins is composed of three members sharing a highly homologous domain, the cyclin box (coded by exons 1-3), which is responsible for their redundant role in the phosphorylation of the retinoblastoma protein upon association with cydin-dependent kinases Cdk4/6. Both mature T and B-cells have a remarkable division capability after antigen stimulation, essential to the generation of efficient immune responses, raising the interest of D Cyclins in lymphopoiesis. Cyclin Dl, although weakly expressed by lymphocytes, is the D Cyclin most commonly implicated in lymphoid cancers and as having a Cdk-independent transcriptional role. To study the role of Cyclin Dl, we used mice deficient for the Dl cyclin box but sparing exons 4-5. Surprisingly, individual mice have very different phenotypes that we subdivided into four arbitrary groups. Group I mice show the most precocious block in lymphoid lineage differentiation, illustrated by a low cellularity of common lymphoid progenitor cells (CLP). The thymi showed very few CD4*CD8*, double positive (DP) cells, while the CD4 CD8TCR, triple negative (TN) populations were found to be mostly constituted by the early CD44*CD25' (TNI) and few CD44*CD25* (TN2). TNl's early thymocyte progenitors (ETP) were virtually absent. At the B-cell lineage level in the bone marrow (BM) there was a major block in pre-proB differentiation. The number of peripheral T-cells was severely reduced, mainly in LN, since group I T-cells lack CCR7 expression. Group II mice presented moderate thymus atrophy. The block on TN differentiation occurs at a later stage, i.e., in the TN3 to TN4 transition, and the TNI population was characterized by a less severe depletion of the ETP. Group II mice showed a partial pre-proB block and a reduction in pre-B-cells. CLPs were also reduced but to a lesser extent than in group I mice. Group ill and group IV mice appear to have a normal thymocyte population distribution but showed an increase on ETP compartment. Group IV mice displayed thymic hyperplasia while group III mice possessed normal thymus cellularity. B-cell differentiation on both groups appeared to be normal but BM precursors had an increase in both CLP and early haematopoietic progenitor's (LSK) levels as compared with wild type mice. Cyclin Dl involvement in G1 to S transition led us to analyse in vivo division rates. Strikingly, group I mice were virtually devoid of cycling cellsin all lymphoid compartments, explaining why lymphoid lineage cells do not differentiate in these mice. In contrast, in all other groups we observed an increased BrdU incorporation. These contradicting phenotypes correlated with the expression or absence of a truncated Dl protein coded by exons 4-5. The presence of the cyclin Dl truncated mRNA was not found in group I mice but high levels of expression are consistently observed in the remaining groups. In the absence of the Dl truncated protein only trace values of Cyclins D2 and D3 were found, highlighting the role of this protein as a master D cyclin regulator, which further supports the profound aplasia and arrest in lymphoid lineage division on cells that predominantly express Cyclin D2. These results suggest that, while the function of the Dl cyclin box is redundant, the regulatory domain coded by exons 4-5 is fundamental for lymphopoiesis. Full Dl protein was also eliminated by RNA interference both in vitro and in vivo. These experiments reproduced the phenotype of group I mice. We have developed a lentiviral vector with a truncated Dl (exons 4-5) and conditional knockout (KO) mice by floxing exons 4-5 of cyclin Dl. These tools will allow us to show Cyclin Dl Cdk-independent role as a transcription regulator in lymphopoiesis and to attribute this function to exons 4-5. Understanding how exons 4-5 regulate different transcription factors might be a key in…

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Breast cancer is the fifth most common cause of cancer death in the worldwide. In the past decades, tamoxifen has been used for clinical treatment for breast cancers. The derivatives of compound thiazolidinedione (TZDs) including troglitazone (rezulin) and rosiglitazone (avandia) are also in the stages of clinical trials. But in the earlier research, some studies reported that the use of these drugs was associated with some serious side effects. Cyclin D1 plays an important role in G1/S phase cell cycle progression and in growth factor- or estrogen-induced mammary epithelial cell proliferation. Cyclin D1 overexpression is also found in high percentage (over 30%) of human breast cancers, correlating with poor prognosis. In this study, we used a cyclin D1-ablative drug VGH No.47 to reduce the expression of cyclin D1 in human breast adenocarcinoma cell line MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) and to study its effect on cell proliferation. Our results demonstrated that VGH No.47 decreased the protein stability of cyclin D1. Conversely, VGH No.47 reduced cyclin D1 at both transcriptional level and protein stability in ER-negative MDA-MB-231 cells. We found that VGH No.47 caused G2/M arrested in both breast cancer cell lines. In addition, we tested whether cyclin D1-ablative drug could sensitize breast cancer cells to tamoxifen and TZDs. We expect to lower the dose of tamoxifen, troglitazone or rosiglitazone to reduce the side effects, but the results do not meet our expectation and do not exhibit synergistic effect.

Bochum, Univ., Diss., 2004. / Erscheinungsjahr an der Haupttitelstelle: 2003. Computerdatei im Fernzugriff.

Bochum, Univ., Diss., 2004. / Erscheinungsjahr an der Haupttitelstelle: 2003. Computerdatei im Fernzugriff.

Bochum, Universiẗat, Diss., 2004. / Erscheinungsjahr an der Haupttitelstelle: 2003.

NOGUEIRA, Renato Luiz Maia. Avaliação clínica da corticoterapia intralesional em lesão central de células gigantes dos maxilares : relevância da expressão dos receptores de corticóide e calcitonina, Cox-2, p16 e amplificação da ciclina D1. 2010. 117 f. Tese (Doutorado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2010. / Submitted by denise santos (denise.santos@ufc.br) on 2014-03-26T14:13:09Z No. of bitstreams: 1 2010_tese_rlmnogueira.pdf: 5019298 bytes, checksum: f55a686958684439dd23ff6fbf2b8ddb (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2014-03-26T14:17:53Z (GMT) No. of bitstreams: 1 2010_tese_rlmnogueira.pdf: 5019298 bytes, checksum: f55a686958684439dd23ff6fbf2b8ddb (MD5) / Made available in DSpace on 2014-03-26T14:17:53Z (GMT). No. of bitstreams: 1 2010_tese_rlmnogueira.pdf: 5019298 bytes, checksum: f55a686958684439dd23ff6fbf2b8ddb (MD5) Previous issue date: 2010 / Central Giant Cells Lesion (CGCL) of the jaws is an intra-bone lesion with no predilection for sex and clinically divided into aggressive and non-aggressive subtypes. Histological, it shows as fibrous tissue with fusiform cells, as well as multinucleated giant cells (GC) clusters, he-morrhagic foci and neovascularization. Surgery is the regular treatment option. As new the-rapeutic approaches have been proposed, intralesional glucocorticoid injection is the main option. This paper assesses retrospectively 21 patients presenting CGCL, treated with intrale-sional triamcinolone hexacetonide by using the following protocol: intralesional injection of triamcinolone hexacetonide 20mg/mL, diluted in a solution of lidocain 2% plus epinephrine 1:200000, at a 1:1 proportion; 1mL of this final solution for each 1cm3 of lesion volume was the injected, with a total of 06 injections, one in every 15 days. Four clinical criteria were sta-bilished to evaluate treatment outcome: 1- Clinical regression or stabilization of the lesion; 2- Absence of symptoms; 3- Raising in density on radiographic controls; 4-Increased resistence when injecting the drug intralesionally. It was also performed immunohistochemical assess-ment for glucocorticoid receptor (GCR) expression, calcitonin receptor (CTR) expression, COX-2 expression, p16 expression and Ciclin D1 gene amplification by CISH, making com-parisons related to aggressivity and to therapeutic outcome. Eleven out of 21 patients of this study were women, and 10 were men. Nine of the patients had lesion located in the maxilla, 12 in the mandible. Ten patients showed aggressive lesions and 11 non-aggressive lesions. Fifteen patients showed good treatment outcome, four patients showed moderate outcome, and two patients showed negative answer to the treatment. Among the 11 patients with non-aggressive lesions, ten showed good outcome and the other, moderate outcome. Among the ten aggressive lesions, five patients showed good outcome, three patients showed moderate outcome and the remaining two patients showed negative answer to the treatment. None of them showed reicidive in a four to eight years follow-up period. Morphologic analysis found positive correlation between volume density of GC/mm2 and lesion aggressiveness, as well as significant reduction in number of GC/mm2 after treatment. Among the markers, only GCR in GC showed statistical relevance associated to the treatment. CTR was espresse in GC and in mononuclear cells in a varying way; p16 was expressed in 30% of the sample; COX-2 was not expressed at all in lesion samples and 33% of the sample showed gene amplification in Ciclin D1. None of the markers showed any statistical significant difference related to aggres-siveness nor to treatment outcome, except for GCR. The study showed the feasibility of the adopted treatment, with tendency to better outcomes in non-aggressive lesion, if compared to the aggressive ones. It also showed evidence pointing to GCR expression in GC as a reliable parameter to predict therapeutic responsiveness to glucocorticoids; and it showed that 33% of CGCL have neoplastic behaviour by Ciclin D1 gene amplification. / A Lesão Central de Células Gigantes dos maxilares (LCCG) é intra-óssea, não tem predileção por sexo, classifica-se em agressivas e não-agressivas, histologicamente consistem tecido fi-broso e celularizado fusiforme associado a células gigantes multinucleadas (CGM), focos de hemorragia e neovascularização, tendo na cirurgia seu habitual tratamento. Novas abordagens terapêuticas foram propostas, sendo a principal delas o uso de corticóides intralesionais. Este trabalho analisa retrospectivamente 21 pacientes portadores de LCCG que foram tratados por hexacetonido de triancinolona intralesional, através do seguinte protocolo: injeção de hexace-tonido de triancinolona 20mg/ml diluído na solução anestésica de lidocaína 2%/epinefrina 1:200.000 numa proporção de 1:1; infiltrando 1ml de solução para cada 1cm3 de lesão, totali-zando 06 aplicações em intervalos quinzenais. Estabeleceu-se 04 critérios clínicos para classi-ficar a resposta ao tratamento: 1- estabilização ou regressão clínica da lesão 2- ausência de sintomas 3- aumento da densidade nos controles radiográficos 4- aumento da resistência a infiltração intralesional da droga, bem como, fez-se uma análise imunohistoquímica quanto à expressão dos Receptores de corticóides (GCR) e Calcitonina (CTR), Cox-2, proteína p16 e amplificação gênica da Ciclina D1 por CISH, comparando quanto a agressividade e a resposta terapêutica a corticoterapia intralesional. Dos 21 pacientes incluídos neste estudo, 11 eram homens e 10 mulheres, 09 tinham lesão em maxila, 12 em mandíbula. Dez eram lesões agres-sivas e 11 não-agressivas, 15 (71,4%) apresentaram uma boa resposta ao tratamento, 04(19%) moderada e 02(9,1%) negativa. Das 11 não agressivas, 10(90,9%) apresentaram boa resposta e 01 (9,1%) resposta moderada, das 10 agressivas 05(50%), 03(30%) e 02(20%) apresentaram boa, moderada e negativa resposta respectivamente, nenhuma apresentou recidiva após o tra-tamento, com preservação que variou entre 04 a 08 anos. Os achados histopatológicos mos-traram uma redução da densidade e do tamanho das CG, e um estroma fibro-colagenoso das lesões. Dentre os marcadores pesquisados, apenas GCR em CG antes do tratamento mostrou significância estatística (p<0,004) com relação a uma boa resposta terapêutica. O CTR ex-pressou-se em células gigantes e mononucleares de forma variada. A p16 apresentou-se ex-pressa em 30% da amostra, COX2 não apresentou expressão na lesão e 33% da amostra apre-sentou amplificação gênica da ciclina D1. Não mostraram significância estatística nem quanto à agressividade, nem quanto resposta ao tratamento, nenhum dos marcadores, exceto o GCR. O estudo mostrou que a corticoterapia intralesional é efetiva e segura para o tratamento das LCCG, com tendência a melhor resposta nas lesões não-agressivas do que nas agressivas. Mostrou ainda que a marcação para GCR em CG demonstrou ser um parâmetro confiável para prever a resposta à terapêutica com a corticoterapia intralesional e que 33% das LCCG têm comportamento neoplásico pela amplificação gênica da ciclina D1.

ALMEIDA, Dennys Ramon de Melo Fernandes. Expressão imunoistoquímica de P16, ciclina D1 e KI67 em lesões orais. 2014. 68 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2014. / Submitted by denise santos (denise.santos@ufc.br) on 2016-03-09T13:58:01Z No. of bitstreams: 1 2014_dis_drmfalmeida.pdf: 1731255 bytes, checksum: 803c0d6d948cc1d74b8edb3cb2d0c18f (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2016-03-09T15:46:29Z (GMT) No. of bitstreams: 1 2014_dis_drmfalmeida.pdf: 1731255 bytes, checksum: 803c0d6d948cc1d74b8edb3cb2d0c18f (MD5) / Made available in DSpace on 2016-03-09T15:46:29Z (GMT). No. of bitstreams: 1 2014_dis_drmfalmeida.pdf: 1731255 bytes, checksum: 803c0d6d948cc1d74b8edb3cb2d0c18f (MD5) Previous issue date: 2014 / P16 is a tumor suppressor gene widely studied in lesions associated with human papillomavirus (HPV) since its overexpression is caused by viral protein E7. Furthermore, this molecule can interact with cyclin D1, an important regulator of cell cycle used a marker of tumor aggressiveness. The expression of the human Ki-67 protein is strictly associated with cell proliferation and consequently the degree of malignancy and prognosis of tumors. This study aimed to evaluate the immunohistochemical expression of p16, cyclin D1 and Ki67 in benign oral lesions showing Koilocytosis and squamous cell carcinoma (CEC) with or without microscopic evidence of viral infection. This is a retrospective study, quantitative and cross carried by lifting paraffin blocks performed in Oral Pathology Laboratory of the course of the Federal University of Ceará Dentistry, from 2008 to 2013. We selected 89 samples grouped in 25 fibroepithelial hyperplasia with Koilocytosis (HFE / Col); 16 oral squamous papillomas (PO); 28 oral squamous cell carcinomas (CEC), subdivided among patients younger than 50 years (CEC-50) and above 50 years (CEC + 50). Were used in 20 cases of fibroepithelial hyperplasia (HFE) as a negative control. In histological review of all groups, except for CEC + 50, cytological changes were found consistent with Koilocytosis (p <0.001). Females were the most prevalent in the whole sample is not, however, statistically significant (p = 0.830). The most affected age groups, in all groups, were the fourth and fifth decades of life, however, without statistical significance (p = 0701). The most common anatomical location in the HFE / Col was the alveolar ridge followed by buccal mucosa in the mouth floor PO and alveolar ridge, the CEC under age 50 the tongue and palate and in cases of CEC over 50 years the tongue, this last significantly (p = 0.015). All benign oral lesions and the group of CEC-50 showed high immunostaining for p16 and cyclin D1, which was statistically significant compared to the negative control (HFE) (p <0.001). The quantitative expression of Ki67 was significantly higher in CEC-50 in the control group (HFE) (p <0.001). We conclude that oral lesions with Koilocytosis (papilloma, HFE / Col and CEC-50) are positive for p16 and cyclin D1 suggests a possible association of pathogenesis with human papillomavirus. / O p16 é um gene supressor de tumor amplamente estudado nas lesões associadas ao Papilomavírus Humano (HPV) visto que sua superexpressão é causada pela proteína viral E7. Além disso, esta molécula pode interagir com ciclina D1, importante regulador do ciclo celular, utilizado como marcador de agressividade tumoral. A expressão da proteína humana Ki67 está estritamente relacionada com a proliferação celular e consequentemente com o grau de malignidade e prognóstico das neoplasias. O presente estudo objetivou avaliar a expressão imunoistoquímica de p16, ciclina D1 e Ki67 em lesões orais benignas exibindo coilocitose e no carcinoma de células escamosas (CEC) com ou sem evidência microscópica de infecção viral. Trata-se de um estudo retrospectivo, quantitativo e transversal realizado por meio do levantamento de blocos parafinados realizado no Laboratório de Patologia Bucal do curso de Odontologia da Universidade Federal do Ceará, no período de 2008 a 2013. Foram selecionadas 89 amostras agrupadas em: 25 hiperplasias fibroepiteliais com coilocitose (HFE/Col); 16 papilomas escamosos orais (PO); 28 carcinomas de células escamosas orais (CEC), subdividido entre pacientes abaixo de 50 anos (CEC-50) e acima de 50 anos (CEC+50). Utilizaram-se 20 casos de hiperplasias fibroepiteliais (HFE) como controle negativo. Na revisão histológica de todos os grupos, exceto no CEC+50, foram encontradas alterações citológicas consistentes com coilocitose (p<0.001). O sexo feminino foi o mais prevalente em toda a amostra não sendo, contudo, estatisticamente significante (p=0.830). As faixas etárias mais afetadas, em todos os grupos, foram a quarta e a quinta décadas de vida, no entanto, sem significância estatística (p=0.701). A localização anatômica mais frequente no HFE/Col foi o rebordo alveolar seguida da mucosa jugal, no PO o assoalho bucal e rebordo alveolar, no CEC abaixo de 50 anos a língua e palato e nos casos de CEC acima de 50 anos a língua, este último de forma significante (p=0.015). Todas as lesões orais benignas e o grupo de CEC-50 apresentaram elevada imunomarcação para p16 e ciclina D1, sendo estatisticamente significante em relação ao controle negativo (HFE) (p<0.001). A expressão quantitativa por Ki67 foi significantemente maior no CEC-50 em relação ao grupo controle (HFE) (p<0.001). Conclui-se que as lesões orais com coilocitose (papiloma, HFE/Col e CEC-50) apresentam positividade para p16 e ciclina D1 sugerindo possível associação da patogênese com o papilomavírus humano.

O câncer de próstata é o tumor maligno mais freqüente nos homens com idade superior a 50 anos, excetuando-se os tumores cutâneos. No Brasil estima-se para o ano de 2012 cerca de 60.180 casos novos deste tipo de neoplasia. Os marcadores tumorais permitem fazer o rastreamento do câncer, o diagnóstico diferencial entre uma neoplasia benigna e maligna, a avaliação de prognóstico e o acompanhamento terapêutico, assim como a detecção da recidiva tumoral. Dentre estes marcadores tumorais, tem-se dado muito atenção para as proteínas que mediam e participam da progressão do ciclo celular. A ciclina D1 é uma proteína nuclear de vida curta que é destruída pela via da ubiquitina ATP dependente, e está envolvida na transição celular da fase do ciclo G1 (repouso) para a fase S (síntese) tanto em células normais como em células neoplásicas. A super expressão de ciclina D1 remove a regulação normal do ciclo celular causando proliferação celular descontrolada, um crescimento anormal dos tecidos e a transformação para um fenótipo neoplásico, atuando como oncogene. No presente trabalho foi estudado a expressão de ciclina D1 em adenocarcinomas de próstata, tendo como objetivo avaliar a relação desta proteína com parâmetros epidemiológicos, clínicos e histopatológicos. Adicionalmente também foi feita comparação de escore de Gleason e lateralidade tumoral entre biópsias prostáticas com agulha e de prostatectomias radicais. No ensaio para ciclina D1 foram analisados 85 casos através de imunoistoquímica (IHQ) de material proveniente de prostatectomias radicais diagnosticados com adenocarcinoma de próstata entre os anos de 2005 e 2010 em nosso serviço. O método de avaliação se utilizou de microscopia ótica comum e contagem semi-quantitativa, comparado-se a expressão com achados clínicos, epidemiológicos e histopatológicos utilizando-se Teste T de Fisher, Qui Quadrado, Mann-Whitney, Curva ROC e correlação de Spearman. Os resultados demonstraram correlação positiva de ciclina D1 com escore de Gleason (p<0,05), com volume prostático (p=0,01) e uma tendência a correlação positiva com invasão perineural (p=0,07). Não houve correlação estatística entre ciclina D1 e o aumento de PSA, assim como outros achados histopatológicos. As biópsias prostáticas com agulha apresentaram subestimação em 40% dos casos para escore de Gleason e de 62,3% dos casos para lateralidade tumoral quando comparadas a prostatectomia radical. Já que as taxas de subestimação de escore de Gleason e lateralidade tumoral são relativamente altas e visto a urgência em se padronizar novos biomarcadores para o câncer prostático, sugerimos que ciclina D1 pode ser utilizada como biomarcador em patologia cirúrgica da próstata auxiliando numa gradação histológica mais precisa em biópsias com agulha colaborando para melhor vigilância e escolha terapêutica. / Prostate cancer is the most common malignant tumor in men older than 50 years, except for skin tumors. In Brazil it is estimated for the year 2012 about 60,180 new cases of this type of neoplasm. Tumor markers allow to cancer screening, differential diagnosis between a benign and malignant, assessment of prognosis and therapeutic monitoring, and detection of tumor recurrence. Among these tumor markers, has been given much attention for proteins that mediate and participate in cell cycle progression. Cyclin D1 is a short-lived nuclear protein that is destroyed by the ATP ubiquitin dependent pathway, and is involved in the transition of cell cycle G1 phase (resting) to the S phase (synthesis) cells both in normal and neoplastic cells. The overexpression of cyclin D1 removes the normal regulation of cell cycle causing uncontrolled cell proliferation, abnormal growth of tissues and transformation to a neoplastic phenotype, acting as an oncogene. In the present work we studied the expression of cyclin D1 in prostate adenocarcinomas, and to evaluate the relationship of this protein with epidemiologic factors, clinical and histopathological features. Additionally comparison was also made of Gleason score and laterality between tumor biopsies and prostate needle radical prostatectomies. In the assay for cyclin D1 were 85 cases analyzed by immunohistochemistry (IHC) of material from radical prostatectomies diagnosed with prostate adenocarcinoma between the years 2005 and 2010 at our institution. The evaluation method utilized were light microscopy and semi-quantitative score, comparing the cyclin D1 expression with clinical, epidemiological and histopathological features using Fisher\'s exact test, chi square test, Mann-Whitney test, ROC curve and Spearman correlation. The results showed a positive correlation of cyclin D1 with Gleason score (p <0.05), prostate volume (p = 0.01) and a trend toward positive correlation with perineural invasion (p = 0.07). There was no statistical correlation between cyclin D1 and increased PSA, as well as other histopathologic features. Prostate needle biopsies showed underestimation in 40% of cases for Gleason score and 62.3% of cases for tumor laterality when compared to radical prostatectomy. Since the rates of underestimation of Gleason score and tumor laterality are relatively high and the urgency to standardize new biomarkers for prostate cancer, we suggest that cyclin D1 may be used as biomarkers in surgical pathology of the prostate assisting more accurate histological grading in needle biopsies and collaborating for better surveillance and therapeutic choice.

O câncer de próstata é o tumor maligno mais freqüente nos homens com idade superior a 50 anos, excetuando-se os tumores cutâneos. No Brasil estima-se para o ano de 2012 cerca de 60.180 casos novos deste tipo de neoplasia. Os marcadores tumorais permitem fazer o rastreamento do câncer, o diagnóstico diferencial entre uma neoplasia benigna e maligna, a avaliação de prognóstico e o acompanhamento terapêutico, assim como a detecção da recidiva tumoral. Dentre estes marcadores tumorais, tem-se dado muito atenção para as proteínas que mediam e participam da progressão do ciclo celular. A ciclina D1 é uma proteína nuclear de vida curta que é destruída pela via da ubiquitina ATP dependente, e está envolvida na transição celular da fase do ciclo G1 (repouso) para a fase S (síntese) tanto em células normais como em células neoplásicas. A super expressão de ciclina D1 remove a regulação normal do ciclo celular causando proliferação celular descontrolada, um crescimento anormal dos tecidos e a transformação para um fenótipo neoplásico, atuando como oncogene. No presente trabalho foi estudado a expressão de ciclina D1 em adenocarcinomas de próstata, tendo como objetivo avaliar a relação desta proteína com parâmetros epidemiológicos, clínicos e histopatológicos. Adicionalmente também foi feita comparação de escore de Gleason e lateralidade tumoral entre biópsias prostáticas com agulha e de prostatectomias radicais. No ensaio para ciclina D1 foram analisados 85 casos através de imunoistoquímica (IHQ) de material proveniente de prostatectomias radicais diagnosticados com adenocarcinoma de próstata entre os anos de 2005 e 2010 em nosso serviço. O método de avaliação se utilizou de microscopia ótica comum e contagem semi-quantitativa, comparado-se a expressão com achados clínicos, epidemiológicos e histopatológicos utilizando-se Teste T de Fisher, Qui Quadrado, Mann-Whitney, Curva ROC e correlação de Spearman. Os resultados demonstraram correlação positiva de ciclina D1 com escore de Gleason (p<0,05), com volume prostático (p=0,01) e uma tendência a correlação positiva com invasão perineural (p=0,07). Não houve correlação estatística entre ciclina D1 e o aumento de PSA, assim como outros achados histopatológicos. As biópsias prostáticas com agulha apresentaram subestimação em 40% dos casos para escore de Gleason e de 62,3% dos casos para lateralidade tumoral quando comparadas a prostatectomia radical. Já que as taxas de subestimação de escore de Gleason e lateralidade tumoral são relativamente altas e visto a urgência em se padronizar novos biomarcadores para o câncer prostático, sugerimos que ciclina D1 pode ser utilizada como biomarcador em patologia cirúrgica da próstata auxiliando numa gradação histológica mais precisa em biópsias com agulha colaborando para melhor vigilância e escolha terapêutica. / Prostate cancer is the most common malignant tumor in men older than 50 years, except for skin tumors. In Brazil it is estimated for the year 2012 about 60,180 new cases of this type of neoplasm. Tumor markers allow to cancer screening, differential diagnosis between a benign and malignant, assessment of prognosis and therapeutic monitoring, and detection of tumor recurrence. Among these tumor markers, has been given much attention for proteins that mediate and participate in cell cycle progression. Cyclin D1 is a short-lived nuclear protein that is destroyed by the ATP ubiquitin dependent pathway, and is involved in the transition of cell cycle G1 phase (resting) to the S phase (synthesis) cells both in normal and neoplastic cells. The overexpression of cyclin D1 removes the normal regulation of cell cycle causing uncontrolled cell proliferation, abnormal growth of tissues and transformation to a neoplastic phenotype, acting as an oncogene. In the present work we studied the expression of cyclin D1 in prostate adenocarcinomas, and to evaluate the relationship of this protein with epidemiologic factors, clinical and histopathological features. Additionally comparison was also made of Gleason score and laterality between tumor biopsies and prostate needle radical prostatectomies. In the assay for cyclin D1 were 85 cases analyzed by immunohistochemistry (IHC) of material from radical prostatectomies diagnosed with prostate adenocarcinoma between the years 2005 and 2010 at our institution. The evaluation method utilized were light microscopy and semi-quantitative score, comparing the cyclin D1 expression with clinical, epidemiological and histopathological features using Fisher\'s exact test, chi square test, Mann-Whitney test, ROC curve and Spearman correlation. The results showed a positive correlation of cyclin D1 with Gleason score (p <0.05), prostate volume (p = 0.01) and a trend toward positive correlation with perineural invasion (p = 0.07). There was no statistical correlation between cyclin D1 and increased PSA, as well as other histopathologic features. Prostate needle biopsies showed underestimation in 40% of cases for Gleason score and 62.3% of cases for tumor laterality when compared to radical prostatectomy. Since the rates of underestimation of Gleason score and tumor laterality are relatively high and the urgency to standardize new biomarkers for prostate cancer, we suggest that cyclin D1 may be used as biomarkers in surgical pathology of the prostate assisting more accurate histological grading in needle biopsies and collaborating for better surveillance and therapeutic choice.