Thesis (Ph. D.)--University of Virginia, 2008. / Includes bibliographical references. Also available online through Digital Dissertations.

Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5301. Adviser: Eric Boerwinkle. Includes bibliographical references.

Source: Masters Abstracts International, Volume: 46-01, page: 0344. Adviser: Patricia Dolan Mullen. Includes bibliographical references (leaves xx-xx).

Prostate cancer increases its incidence with age after men in their fifth decade as the ratio of estrogen to androgen rises. Epidemiological studies indicated that high levels of estrogens are associated with the high-risk ethnic groups for prostate cancer. Therefore, estrogens may be involved in prostatic carcinogenesis. It is widely believed that the actions of estrogens are mediated by estrogen receptors. However, expression of estrogen receptor in normal prostate and lesions of the gland was controversial. With the recent discovery of second estrogen receptor (ER-β), this issue became more complicated and it needs to be readdressed. In addition, the biological involvement of ER-β in human prostate remains to be investigated. In this study, we demonstrated that human normal prostate epithelial cells express ER-β but not ER-α, suggesting that estrogens act directly on these epithelial cells via ER-β. Using RT-PCR analysis, the transcripts of ER-β were detected in our primary human prostatic epithelial cell cultures that were derived from the ultrasound-guided peripheral zone biopsies and the cells express two estrogen-regulated genes such as progesterone receptor (PR) and pS2. Moreover, we had developed an ER-β antibody with fully characterizations and used it for immunohistochemistry. Results indicated that ER-p protein is expressed in the basal compartment of prostatic epithelium of the gland. Our findings lead to a new hypothesis that estrogens directly act on human prostatic epithelial cells to modulate its biological functions. To investigate expression of ERs in prostate cancer, RT-PCR analysis was used. We found that all three human prostate metastatic cancer cell lines, DU145, PC-3 and LNCaP, express ER-β transcripts while ER-α mRNA expression only in PC-3 cells. Expressions of PR and pS2 in these cell lines are various. LNCaP cells express both PR and pS2 mRNAs but DU145 cells with only PR and PC-3 cells with only pS2. Our immunohistochemical results on prostatic lesions revealed down-regulation of ER-β expression in high-grade of dysplasia and carcinoma of peripheral zone of the prostate compared to their low-grade lesions. This down-regulation in high-grade carcinoma was verified in transcriptional level by RT-PCR analysis on micro dissected normal epithelium and lesion samples of the gland. In the metastasis, ER-β was found to be reactivated as we observed ER-β mRNA expression in prostate cancer cell lines. Recent evidence suggests that ER-β may be antiproliferative factor for a protective effect against the mitogenic activity of estrogens in breast and androgens in prostate. Activation of the receptor may exhibit cell growth inhibition. We demonstrated that antiestrogens [ICI-182,780 (ICI) and 4-hydroxytamoxifen], raloxifene and phytoestrogen (resveratrol), but not estrogens (17β-estradiol and diethylstilbestrol), inhibit growth of DU145 cells which express only ER-β while PC-3 cells with both ERs showed growth inhibition in response to estrogen and antiestrogen treatments. In DU145 cells, the ICI-induced cell growth inhibition was prevented by blockade of ER-β expression using antisense oligonucleotide. It indicated that the inhibition is mediated via ER-p associated pathway. Using flow cytometry, we found that ICI-treatment could induce accumulation of cells at GO-G1 phase of cell cycle. Similarly, this GO-G1 cell accumulation was also induced by raloxifene in DU145 cells. For resveratrol, the treatment exhibited dual effects on cell cycle distribution in DU145 cells. In the early treatment, resveratrol induced cell cycle arrests at GO-G1phase. The prolonged treatment leads to S-phase cell cycle arrest. To study the molecular mechanism of this ER-p associated cell growth inhibition, real-time RT-PCR analysis was used to semi-quantitate the transcript levels of tentative ER-β regulated genes such as telomerase reverse transcriptase (TERT), survivin and thymidylate synthase (TS) in the treated cells compared to those in control. Results demonstrated that the treatment of ICI could down-regulate TERT and survivin mRNA expressions with dose-dependent fashion. As the ICI-treatment, resveratrol downregulated expression levels of TERT, survivin and TS in DU145 cells. Down-regulation of TS may be related to the S-phase cell cycle arrest observed in the prolonged treatment of resveratrol. Taken together, our findings support the concept that ER-β participates in cell cycle regulation in normal and malignant prostatic epithelial cells. Presence of ER-β in basal cells of the prostate acini indicates that the direct actions of estrogens may be involved in the normal physiology of the gland. Loss of this receptor in primary prostate cancer and its re-expression in metastasis suggests the roles of ER-β in the cancer progression. Activation of the receptor by antiestrogen and phytoestrogen induced cell growth inhibition in prostate cancer cells. The mechanism may be mediated by reduction of cell survival factors and eventually decrease in cell viability and induction of cell cycle arrests.

INTRODUÇÃO - O câncer de próstata é a doença maligna mais diagnosticada no mundo, desconsiderando os tumores de pele. A prostatectomia radical tem sido considerada a opção terapêutica preferida no tratamento do câncer clinicamente localizado. O conhecimento da anatomia neurovascular da próstata é de extrema importância para a obtenção de resultados funcionais satisfatórios sem prejuízo aos fins oncológicos. A maioria dos estudos anatômicos já publicados utilizou próstatas removidas cirurgicamente - espécime de prostatectomia radical. Estudos realizados com próstata de cadáveres são importantes por permitir a ressecção em bloco dos órgãos pélvicos, possibilitando uma melhor avaliação da neuroanatomia periprostática. O objetivo deste estudo é avaliar detalhadamente a distribuição das fibras nervosas periprostáticas em cadáveres humanos. MÉTODOS - Foram obtidos 10 blocos viscerais de cadáveres com idade superior a 50 anos constituídos por bexiga, próstata e fáscias adjacentes, uretra proximal e reto. Após fixação em formalina, o bloco visceral foi fatiado transversalmente em fatias de aproximadamente 5 mm. Cada fatia foi dividida em quatro setores, tendo a uretra como eixo central e encaminhada para inclusão em parafina, secção com micrótomo padrão e confecção das lâminas coradas em HE. A cápsula prostática (CP) foi identificada e demarcada e áreas de avaliação foram definidas conforme distância da CP, designadas como distância D1(até 2,5 mm), D2 (2,5 a 5 mm) e D3(maior de 5 mm). Em cada região da próstata (região apical, região média e região basal) as fibras nervosas foram avaliadas de acordo com a distribuição circunferencial nos segmentos anterior, ântero-laterais direito e esquerdo, póstero-laterais direito e esquerdo e posterior e conforme a distância da CP - distâncias D1, D2 e D3. RESULTADOS - Foram identificados 29.275 fibras nervosas, das quais 3.274 (11,18%) foram detectados na região apical, 11.997 (40,98%) na região média e 14.004 (47,84%) na região basal da próstata. Na região basal, aproximadamente, 46% das fibras nervosas foram identificadas nas faces póstero-laterais, 20% na face posterior da próstata e menos de 9% na face anterior. Houve predomínio numérico de FN nas áreas mais distantes, com 46,62% delas sendo identificadas em D3. Na região média, 45% das fibras nervosas se distribuíram nos segmentos anteriores a ântero-laterais. Cerca de 45% se distribuíram igualmente nas faces póstero-laterais direita e esquerda e apenas 10% na face posterior. Nesta região, observou-se que mais de 60% das FN estavam dispostas nas áreas D1. Na região apical, também se observou predomínio de fibras nervosas nos segmentos que compõem as faces posteriores e póstero-laterais (61%). Aproximadamente, 24% das FN se distribuíram igualmente entre as faces ântero-laterais direita e esquerda e quase 15% estavam distribuídas na face anterior do ápice prostático. Mais da metade delas encontravam-se distribuídas a até 2,5 mm da cápsula prostática. Nos segmentos anteriores e ântero-laterais, o predomínio de FN nas áreas D1 foi mais acentuado do que nos outros segmentos. Na avaliação geral, a quantidade relativa de fibras nervosas identificadas nas áreas D1 variou de maneira inversamente proporcional à quantidade relativa de FN das áreas D3. Nas áreas demarcadas entre 2,5 mm e 5 mm da CP (D2), a quantidade relativa de fibras nervosas se manteve relativamente constante. CONCLUSÕES - No sentido craniocaudal, a quantidade de fibras nervosas diminui progressivamente, a distribuição circunferencial se modifica, com aumento da quantidade relativa de fibras nervosas nas faces anteriores e a distribuição em relação à distância da próstata também se modifica, com aumento da quantidade relativa de fibras nervosas nas áreas mais próximas da próstata. A quantidade relativa de fibras nervosas dispostas a uma distância mínima de 2,5 mm da cápsula prostática se mantém constante / INTRODUCTION - Prostate cancer is the most commonly diagnosed malignancy in the world, excluding skin tumors. The incidence of localized tumor increased substantially after the PSA era. Consequently, the percentage of men treated by radical surgery for clinically localized prostate cancer increased. The exact paths of periprostatic nerves have been under debate over the last decades. In the present study, the topographic distribution of nerves around the prostate and their relative distances from the prostatic capsule were analyzed in male cadaver visceral blocs. METHODS - The pelvic organs from ten fresh male cadavers were removed and serial sectioned en bloc for histological investigation. The prostatic capsule was identified, and distances of 2.5 mm and 5 mm from the prostate were demarked with lines. We quantified the number of nerve fibers present in each subsector of each slide and recorded their position relative to the prostatic capsule. RESULTS - A total of 29,275 nerve fibers were identified, of which 3,274 (11.18%) were detected in the apex, 11,997 (40.98%) in the middle and 14,004 (47.83%) in the basal area of the prostate. The majority of nerves were identified in the posterolateral and posterior surfaces of the prostate. At the apical region, the percentage of nerve fibers identified in the anterior region was higher. The nerves identified at the apex were mainly located up to 2.5 mm from the prostate. This proximity to the prostate was specifically observed in the ântero-lateral and anterior sectors. In the craniocaudal sense, the percentage of nerves identified between 2.5 and 5 mm from the prostatic capsule remained constant. CONCLUSIONS - A significant number of nerve fibers were present in the anterior and ântero-lateral positions, especially at the apex. The anterior nerves were closer to the prostate. This proximity suggests that the anterior nerves may participate in local physiology. It is likely that the safe distance of 2.5 mm from all surfaces of the prostate may be related to cavernous fiber preservation

INTRODUÇÃO: O Câncer de Próstata (CaP) é a sexta neoplasia mais comum no mundo correspondendo a aproximadamente 10% do total de cânceres. No Brasil, o CaP é a neoplasia maligna não cutânea mais comum entre os homens. A hereditariedade é um dos principais fatores de risco do CaP, que se caracteriza pela herança de mutações em genes de susceptibilidade de alta penetrância que quando transmitidos aos descendentes aumentam o risco de desenvolvimento de tumores. Os andrógenos e estrógenos influenciam o desenvolvimento, maturação e manutenção da próstata, afetando a proliferação e a diferenciação. Isso tem despertado grande interesse no papel desses hormônios esteroides no desenvolvimento e manutenção tanto da próstata normal quanto maligna. Os Polimorfismos de Nucleotídeo Único (SNPs) são variantes de risco genéticos associados com uma série de doenças, incluindo o câncer. Considerando que a história familiar e que os componentes hormonais constituem fatores de risco para o desenvolvimento do CaP, acredita-se que a identificação de polimorfismos envolvidos nesses processos possa ter um papel relevante para auxiliar no desenvolvimento de ferramentas alternativas para a detecção precoce e para a definição do prognóstico desta neoplasia. OBJETIVOS: Analisar polimorfismos (SNPs) relacionados com histórico familiar e com fatores hormonais em amostras de sangue de pacientes com CaP e em homens saudáveis. Além disso, correlacionar os resultados da genotipagem com parâmetros clínico-patológicos. MÉTODOS: O estudo foi composto por 185 pacientes diagnosticados com CaP, sendo 97 casos esporádicos e 72 com histórico familiar (dois parentes de primeiro grau). O grupo controle foi composto por 70 amostras de sangue de indivíduos saudáveis, que comprovadamente não possuíam CaP e fazem acompanhamento com intuito preventivo. Foram selecionados 13 polimorfismos para análise: rs10486567, rs10993994, rs9364554, rs5945572, rs2735839, rs4430796, rs7501939, rs138213197, rs1271572, rs2987983, rs8072254, rs4919743 e rs3808330. A genotipagem foi realizada através da técnica de PCR em tempo real (qPCR) e correlacionada com o histórico familiar de CaP, PSA pré-operatório, graduação histológica de Gleason e estadiamento patológico. RESULTADOS: Analisamos a frequência dos polimorfismos selecionados e encontramos as seguintes correlações em nossos casos: os SNPs rs10486567 e rs9364554 aumentam a chance de desenvolvimento do CaP enquanto que o SNP rs8072254 diminui o risco. Com relação à hereditariedade, o SNP rs1271571 apresentou associação com o CaP esporádico. Na comparação com os fatores prognósticos encontramos que o SNP rs3808330 foi mais frequente em indivíduos que possuíam PSA < 10; o SNP rs7501939 foi mais frequente em indivíduos com menor escore de Gleason e ausência de recidiva e o SNP rs5945572 foi mais frequente em indivíduos com menor escore de Gleason na peça. CONCLUSÕES: De uma forma geral encontramos polimorfismos que parecem ter um papel relevante no desenvolvimento do CaP, na transmissão familiar e a fatores prognósticos. Estes importantes polimorfismos, ainda não haviam sido estudados na população brasileira e nosso trabalho identificou correlações ainda não demonstradas na literatura / BACKGROUND: Prostate Cancer (PCa) is the sixth most common cancer worldwide accounting for around 10% of all cancers. In Brazil, the PCa is the most common non-skin malignancy among men. Heredity is one of the main risk factors for PCa, which is characterized by mutations of heritage in highpenetrance susceptibility genes that when transmitted to offspring increase the risk of tumor development. Androgens and estrogens influence the development, maturation and maintenance of the prostate, affect proliferation and differentiation. This has aroused great interest in the role of these steroid hormones in the development and maintenance of both normal and malignant prostate. Single Nucleotide Polymorphisms (SNPs) are variants of genetic risk associated with a number of diseases including cancer. Considering that the family history and hormonal components are risk factors for the development of PCa, we believe that the identification of polymorphisms involved in these processes may have an important role to assist in the development of alternative tools for early detection and to define the prognosis of this cancer. OBJECTIVES: To analyze polymorphisms (SNPs) associated with family history and hormonal factors in patient blood samples with PCa and in healthy men. In addition, to correlate the results of genotyping with clinical-pathological parameters. METHODS: The study consisted of 185 patients diagnosed with PCa, divided into 97 sporadic cases and 72 with a family history. The control group consisted of 70 blood samples from healthy individuals who had no proven PCa and do it for preventive purposes. We selected 13 polymorphisms for analysis: rs10486567, rs10993994, rs9364554, rs5945572, rs2735839, rs4430796, rs7501939, rs138213197, rs1271572, rs2987983, rs8072254, rs4919743 and rs3808330. Genotyping was performed by PCR in real time (qRT -PCR) and correlated with family history of PCa, preoperative PSA, Gleason histologic grading and pathological staging. RESULTS: We analyzed the frequency of the selected polymorphisms and found the following correlations in our cases: SNPs rs10486567 and rs9364554 increase the chance of developing PCa while the SNP rs8072254 decreases the risk. Regarding heredity, the SNP rs1271571 presented association with sporadic PCa. In comparison with the prognostic factors we found that the SNP rs3808330 was more frequent in patients who had PSA < 10; SNP rs7501939 was more frequent in patients with lower Gleason score and no recurrence and the SNP rs5945572 was more frequent in subjects with lower Gleason score on the surgical specimen. CONCLUSIONS: In general we found that polymorphisms that appear to have a relevant role in the development of PCa in family transmission and in prognostic factors. These important polymorphisms had not yet been studied in the Brazilian population and our work has identified correlations yet not demonstrated in the literature

Objetivos: (a) Validar externamente os nomogramas de Crippa e Srougi que combinam antígeno prostático específico (PSA) sérico, porcentagem de fragmentos positivos na biópsia prostática (PFPB) e escore de Gleason da biópsia prostática para predição de doença órgão-confinada (DOC), em prostatectomias radicais realizadas entre 1988 e 2002, em uma população contemporânea de instituição de ensino terciária de assistência pública; (b) Re-derivar as variáveis e ajustá-las para produzir dois nomogramas de predição para DOC e invasão de vesículas seminais (IVS), resultando nos nomogramas da USP. Método: A acurácia (discriminação e calibração) dos nomogramas de Crippa e Srougi foi examinada em 1.002 pacientes submetidos a prostatectomia radical retropúbica (PRR) entre 2005 e 2010 na Universidade de São Paulo. Curvas ROC com as respectivas áreas sob a curva (ASC) e escores de Brier foram usados para quantificar as propriedades discriminativas das predições dos nomogramas de Crippa e Srougi para DOC. Gráficos LOESS de calibração foram usados para expressar visualmente a relação entre as probabilidades preditas e as taxas de desfecho observadas. Na sequência, rederivação das variáveis incluindo PSA, PFPB, escore de Gleason da biópsia prostática e estádio clínico foi realizada para os desfechos DOC e IVS. Modelos finais de regressão logística originaram os nomogramas de predição para DOC e IVS (intervalos de confiança de 95% em 1.000 amostras bootstrap). Os procedimentos de validação acima descritos foram aplicados na validação interna dos nomogramas da USP. Resultados: Os nomogramas de Crippa e Srougi para predição de DOC apresentaram ROC ASC=0,68 (IC: 0,65-0,70), escore de Brier de 0,17 e considerável subestimação nos gráficos LOESS. Os nomogramas da USP apresentaram ROC ASC=0,73 (IC: 0,70- 0,76) e escore de Brier de 0,16 para DOC e ROC ASC=0,77 (IC: 0,73-0,79) e escore de Brier de 0,08 para IVS. Os gráficos LOESS mostraram excelente calibração para DOC e considerável superestimação de desfecho para IVS em todas as faixas de predição acima de 2%. Conclusões: Os nomogramas de Crippa e Srougi foram validados externamente apresentando discriminação moderada e considerável subestimação de desfecho para DOC. Os nomogramas da USP apresentaram boa discriminação para DOC e IVS, excelente calibração para DOC e considerável superestimação de desfecho para IVS / Purposes: (a) To externally validate the Crippa and Srougi nomograms that combine serum prostate-specific antigen (PSA), percent of positive biopsy cores (PPBC), and biopsy Gleason score to provide the likelihood of organ-confined disease (OCD) in radical prostatectomy performed between 1988 and 2002 in a contemporary cohort of a public health environment of a teaching institution; (b) To re-derivate the variables and adjust them to produce two predictive nomograms for OCD and seminal vesicle invasion (SVI), the USP nomograms. Material and Methods: The discrimination and calibration properties of the nomograms from Crippa and Srougi in 1002 men who underwent radical prostatectomy between 2005 and 2010 at the University of Sao Paulo (USP) were examined. The ROC derived area under the curve (AUC) and the Brier score were used to quantify the discriminant properties of the predictions of that nomograms for OCD. LOESS based calibration plots were used to examine the relationship between the predicted and observed rates of OCD. Furthermore, variables re-derivation including PSA, PPBC, biopsy Gleason score and clinical stage was done for OCD and SVI outcomes. Logistic regression final models resulted in predictive nomograms for OCD and SVI (1000 bootstrap 95% confidence intervals). The abovementioned validation procedures were applied in USP nomograms internal validation. Results: The OCD prediction nomograms from Crippa and Srougi showed ROC AUC = 0.68 (CI:0.65-0.70) and Brier score of 0.17; and considerable underestimation in LOESS plots. The USP nomograms showed ROC AUC=0.73 (CI:0.70-0.76) and Brier score of 0,16 for OCD and ROC AUC=0.77 (CI: 0.73-0.79) and Brier score of 0,08 for SVI. The LOESS plots showed excellent calibration for OCD and overestimation for SVI in all prediction ranges over 2%. Conclusions: The nomograms from Crippa and Srougi were externally validated showing moderate discrimination and considerable OCD underestimation. The USP nomograms showed good discrimination for both, OCD and SVI, excellent calibration for OCD and considerable overestimation for SVI

Abstract Human prostate-specific antigen (hPSA, KLK3) and glandular kallikrein 2 (hK2, KLK2), two members of a large human tissue kallikrein enzyme family, were produced as recombinant mature proteins for the first time and characterized. Furthermore, their association with prostate cancer was studied. Both proteins were produced with baculovirus expression vector system in pilot-scale using bioreactors. Recombinant hPSA was either active with chymotrypsin-like activity or inactive with incorrect processing of N-terminus. The molecular weight of active recombinant hPSA was 31 kD and it formed stable complexes with serine protease inhibitors, α1-antichymotrypsin (ACT) and α2-macroglobulin (2αM). Two polymorphic forms of KLK2, Arg226hK2 and Trp226hK2, were found. The recombinant Arg226hK2 had trypsin-like activity, while recombinant Trp226hK2 was inactive. The Arg226hK2 was labile with low production yields. The molecular weights of hK2 polymorphic forms were 33 kD. hPSA isoforms secreted by prostate cancer cells, LNCaP, were isolated and characterized. These proteins were N-terminally heterogeneous: 10-60% of LNCaP-PSAs were correctly processed. Molecular modeling suggested that the additions or deletions of two or four N-terminal amino acids could affect the three-dimensional structure and reduce the activity of LNCaP-PSA. Active isoforms had chymotrypsin-like activity and formed stable complexes with ACT and 2αM. The expression of hPSA and hK2 was studied with in situ hybridization and immunohistochemistry techniques in benign and cancerous prostate tissue. hK2 mRNA was expressed at a significantly higher level in prostate cancer tissue than in benign prostate tissue (P &lt; 0.0005). The hPSA mRNA expression levels were reversed (P = 0.06). In benign tissue, the mean level of hK2 mRNA was 82% of the respective value of hPSA (P &lt; 0.003), whereas in tumor tissue the mean hK2 expression level was 21% higher than that of hPSA (P &lt; 0.01). The results at protein level supported the mRNA findings. There was a correlation between hPSA and hK2 mRNA levels in both benign (r = 0.735; P &lt; 0.01) and malignant (r = 0.767; P &lt; 0.01) prostate tissue. It was shown with competitively differential PCR that the KLK2 gene was amplified in prostate tumor tissue, while the KLK3 gene was not. These results suggest that hK2 and hPSA have a diverse value in the diagnosis of prostate cancer.

Ce travail de recherche translationnelle a pour objectif de corréler les données de l'imagerie anatomique et fonctionnelle, aux facteurs pronostiques cliniques, biologiques, histologiques, moléculaires du cancer de prostate. Nos travaux ont permis de montrer que l'IRM prostatique permettait de détecter et de stratifier le risque de cancer de prostate dit "significatif", que l'IRM couplée aux biopsies prostatiques ciblées permettait d'identifier plus de cancers de prostate significatifs que les biopsies dites "systématiques", que l'IRM donnait des informations sur l'agressivité du cancer de prostate définie in situ par les marqueurs histologiques et moléculaires, que cette information était plus juste que celle obtenue par la stratégie diagnostique actuelle du dosage de PSA et des biopsies prostatiques qui sous estiment l'agressivité tumorale, qu'il existait cependant des formes de cancer dont l'agressivité ne pouvait être déterminée ni par l'imagerie, ni par l'analyse histologique standard mais seule par une analyse moléculaire. / This study represents a translational research with the objective to identify prognostic biomarkers in prostate cancer (PCa) by means of a radio-genomics strategy that integrates gene expression, biology, histology, and medical images. Our results show that; multiparametric MR imaging of the prostate provide clinically relevant stratification of the risk of showing prostate cancer ; that MRI/TRUS-fusion imaging protocol with limited targeted biopsies detected more men with clinically significant PCa, that we were able to confirm that functional MRI (diffusion) and morphologic MRI (Tmax) were well correlated with tumor aggressiveness as defined by Gleason score and genomic score, that the ADC values of suspicious areas on prostate MR imaging are strongly correlated with post-surgical Gleason score, that ADC values performed significantly better than TRUS biopsy Gleason scores for the prediction of prostate cancer aggressiveness as defined by prostatectomy Gleason score or by Ki-67 proliferation index.

Orientador: Miriam Dambros Lorenzetti / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T00:11:28Z (GMT). No. of bitstreams: 1 Souza_FelipeGoncalvesSchrodere_M.pdf: 1431848 bytes, checksum: df85a182625e0c75b33faa908d302d6c (MD5) Previous issue date: 2015 / Resumo: Introdução: A neoplasia de próstata é a segunda mais prevalente entre os homens, com estimativa de cerca de 68 mil casos novos no Brasil em 2014. Além disso, é a segunda causa de morte no sexo masculino por neoplasias. O câncer de próstata raramente causa sintomas em seus estágios iniciais, por isso existe a necessidade do diagnóstico precoce. Atualmente a forma de rastreamento desta neoplasia ainda é controverso, porém quando realizado, baseia-se em exame digital retal da próstata e na mensuração sérica dos níveis do PSA. Estudos de rastreamento populacional mostraram uma diminuição de 41% no casos de neoplasia avançada de próstata e risco de diagnóstico de câncer 46% maior, quando comparados a grupos não submetidos a rastreamento. O PSA não é câncer específico, então, os refinamentos do PSA (relação do PSA livre/total, densidade do PSA e velocidade do PSA) aparecem como métodos para melhorar sua especificidade, na tentativa de diminuir o número de biópsias desnecessárias. Quando existe suspeita diagnóstica, é indicada uma biópsia guiada por ultrassonografia transretal, procedimento que não é isento de complicações, principalmente as infecciosas. Objetivos: Avaliar a positividade para adenocarcinoma de próstata em biópsias guiadas por ultrassonografia transretal, e estratificá-la de acordo com a idade, com o valor do PSA total, com a densidade do PSA e com a relação entre a fração livre do PSA e o PSA total. Materiais e Métodos: Analisamos retrospectivamente os resultados obtidos no serviço de urologia do Hospital Municipal Dr. Mário Gatti com relação à positividade das biópsias estratificadas pela idade, PSA total, percentual da fração livre do PSA e densidade do PSA, comparando-os com os dados descritos na literatura. Resultados: Foram realizadas 314 biópsias no período de janeiro de 2011 à novembro de 2012. A média de idade dos pacientes foi de 65,2 (± 8,32) anos e a positividade foi de 44,9%. A positividade das biópsias foi maior com o aumento da idade (p<0,001), com o aumento do PSA (p<0,001), com o aumento da densidade (p<0,001) e com a diminuição da relação do PSA (p=0,002) Conclusão: A neoplasia prostática correlacionou-se significativamente com o aumento da idade, do PSA total, da densidade do PSA, e com a diminuição da relação entre o PSA livre sobre o PSA total / Abstract: Introduction: Prostate neoplasia is the second most prevalent neoplasia in men and about 68 thousand new cases were estimated in 2014 in Brazil. In addition, it is the second most common cause of cancer related death in men. Prostate cancer rarely causes symptoms at an early stage, hence the need of an early diagnosis. Although there is still no consensus about how to screen this neoplasia, it is done through digital rectal examination and measurement of PSA levels. Population screening trials showed a decrease of 41% in new cases of advanced prostate neoplasia. The risk of a cancer diagnosis increased 46% when compared to the group who was not screened. PSA is not cancer specific. Therefore, PSA features (relation between free PSA and total PSA, PSA density, PSA velocity) are used to increase its specificity, attempting to reduce the number of unnecessary biopsies. Once there is a cancer suspicion, a biopsy guided by transrectal ultrasonography is indicated, which is not a complication free procedure, mainly infection. Objective: to assess the positiveness of prostatic adenocarcinoma in transrectal ultrasonography guided biopsies and to evaluate it according to age, total PSA value, PSA density, and the relation between free PSA and total PSA. Materials and Methods: This is a retrospective study with patients who underwent prostatic biopsy guided by transrectal ultrasonography done by the urology team from Hospital Municipal Dr. Mário Gatti. Collected data included patient¿s age, total PSA value, PSA density and the relation between free PSA and total PSA. Results: 314 prostatic biopsies guided by transrectal ultrasonography were analyzed between January 2011 and November 2012. Patient¿s mean age was 65.2 (+/-8.32) years. A positive biopsy to adenocarcinoma was found in 44.9% of the patients. The number of positive biopsies was higher among older patients (p<0.001). It was also higher the higher the PSA (p<0.001) and the higher the PSA density (p<0.001). It was inversely related to PSA relation (p=0.002). Conclusion: There is a direct correlation between prostatic neoplasia and age, value of PSA and PSA density. Additionally, prostatic neoplasia is inversely proportional to the relation of free PSA over total PSA / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências da Cirurgia