No mundo inteiro, o carcinoma de próstata ocupa o quinto lugar entre as neoplasias malignas de maior mortalidade. No Brasil, estima-se para o ano de 2001 que, entre os tumores malignos no sexo masculino, o carcinoma de próstata terá a segunda maior taxa de mortalidade e a primeira taxa de incidência (Estimativa da incidência e mortalidade por câncer no Brasil – 2001 – INCA). Uma vez que a taxa de mortalidade por carcinoma de próstata na população brasileira tem aumentado significativamente nos últimos anos, a presente tese se propôs a investigar regiões polimórficas em genes conhecidos que poderiam estar associadas a um aumento na predisposição a esta forma de câncer. Assim sendo, estudamos as regiões polimórficas CAG e GGC do gene do receptor de andrógeno; o polimorfismo C1171T do gene do receptor de vitamina D; o polimorfismo D104N do gene da endostatina; o polimorfismo Pro72Arg do gene p53 e a região polimórfica AAAAC localizada na região 3’ não traduzida do gene MXI1. / In the world’s population prostate carcinoma is the fifth most commom male cancer-related death malignancy. In Brazil, among all male invasive cancers it is expected that prostate carcinoma will have the second highest death rate and the highest incidence rate (Estimativa da incidência e mortalidade por câncer no Brasil, 2001). As the prostate carcinoma death rate in brazilian population has been increasing over the last several years we proposed to investigate polymorphic regions of known genes that might be associated with prostate carcinoma predisposition. We studied the androgen receptor CAG and GGC polymorphic regions, the vitamin D receptor C1171T polymorphism, the endostatin D104N polymorphism, the p53 Pro72Arg polymorphism and the MXI1 AAAAC polymorphic region.

Research on aging indicates that older adults do not, as a group, report decreased health-related quality of life (HRQOL) despite age-related declines in physical health status. Several cognitive adaptation strategies have been suggested to underlie HRQOL stability in this population. Studies of older cancer patients nevertheless show substantial variance in post-treatment HRQOL outcomes, although cognitive mechanisms for individual differences have received little attention. The current study expanded on a developmental adaptation of self-regulation theory in which aging influences both self-vulnerability and perceptions of disease. A model was tested in which older age was hypothesized to predict better HRQOL via less severe illness perceptions in men treated for localized (Stage I and II) PC. Results indicated that age was not directly associated with HRQOL. However, older age was indirectly associated with better HRQOL via less severe PC perceptions. Further, this indirection association helped account for the positive association between age and HRQOL that three risk factors (income, comorbid disease burden, and sexual function) were shown to suppress. Perceptions of PC may promote HRQOL stability by mitigating age-related declines in health and income status. Disease perceptions thus represent critical components of health assessments and interventions for PC survivors of all ages, but particularly for men facing difficulties adapting to complex health profiles or normative lifespan challenges.

No mundo inteiro, o carcinoma de próstata ocupa o quinto lugar entre as neoplasias malignas de maior mortalidade. No Brasil, estima-se para o ano de 2001 que, entre os tumores malignos no sexo masculino, o carcinoma de próstata terá a segunda maior taxa de mortalidade e a primeira taxa de incidência (Estimativa da incidência e mortalidade por câncer no Brasil – 2001 – INCA). Uma vez que a taxa de mortalidade por carcinoma de próstata na população brasileira tem aumentado significativamente nos últimos anos, a presente tese se propôs a investigar regiões polimórficas em genes conhecidos que poderiam estar associadas a um aumento na predisposição a esta forma de câncer. Assim sendo, estudamos as regiões polimórficas CAG e GGC do gene do receptor de andrógeno; o polimorfismo C1171T do gene do receptor de vitamina D; o polimorfismo D104N do gene da endostatina; o polimorfismo Pro72Arg do gene p53 e a região polimórfica AAAAC localizada na região 3’ não traduzida do gene MXI1. / In the world’s population prostate carcinoma is the fifth most commom male cancer-related death malignancy. In Brazil, among all male invasive cancers it is expected that prostate carcinoma will have the second highest death rate and the highest incidence rate (Estimativa da incidência e mortalidade por câncer no Brasil, 2001). As the prostate carcinoma death rate in brazilian population has been increasing over the last several years we proposed to investigate polymorphic regions of known genes that might be associated with prostate carcinoma predisposition. We studied the androgen receptor CAG and GGC polymorphic regions, the vitamin D receptor C1171T polymorphism, the endostatin D104N polymorphism, the p53 Pro72Arg polymorphism and the MXI1 AAAAC polymorphic region.

Many cancers have long been known to display an absolute requirement for the amino acid methionine (L-Met). Studies have shown that in the absence of L-Met, sensitive neoplasms experience cell cycle arrest and perish. Without the metabolic deviations that characterize L-Met auxotrophs, normal cells are able to grow on precursors such as homocysteine and tolerate periods of L-Met starvation. The differential requirement for this amino acid between normal and tumor cells has been exploited through enzymatic serum degradation of L-Met by a bacterial methionine-γ-lyase (MGL). Though MGL was able to deplete L-Met to therapeutically useful levels in animal models and exert a significant cytotoxic effect on malignant cell lines in vitro and on tumor xenografts in vivo, the clinical implementation of this enzyme is hampered by its short serum half-life and potential for catastrophic immune response. In the chapters that follow, we describe the engineering of a novel human methionine degrading enzyme (hMGL) that overcomes the limitations of the bacterial therapeutic. We have shown that hMGL is capable of degrading methionine at a therapeutically useful rate and inducing extensive cell killing in a variety of neoplasms. This enzyme is expected to have low immunogenicity in patients and a high therapeutic index. We have developed a high throughput screen for methionine degrading activity that we can utilize to further engineer the enzyme based on the results of additional preclinical development. We have found that hMGL is also capable of degrading cystine to operate as a dual amino acid depletion treatment that is expected to be more potent than methionine depletion alone. Due to the wide array of neoplasms sensitive to methionine and cystine starvation, the engineered enzyme holds a great deal of promise as a unique and powerful cancer therapeutic. / text

Orientadores: Christine Hackel, Juergen K. V. Reichardt, Maricilda P. Mello / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-10T00:27:44Z (GMT). No. of bitstreams: 1 Ferraz_LucioFabioCaldas_D.pdf: 2604031 bytes, checksum: c313be68a5b9599e035866a8ee12ef8c (MD5) Previous issue date: 2006 / Resumo: O hormônio androgênico di-hidrotestosterona (DHT) possui fundamental importância na diferenciação sexual masculina e no desenvolvimento e manutenção da próstata. Duas enzimas atuam diretamente na concentração deste andrógeno nas células: 1) com uma função anabólica, a enzima 5α-redutase tipo 2 (gene SRD5A2) é responsável pela síntese de DHT ao converter testosterona (T) em 5α-di-hidrotestosterona e 2) com uma função catabólica, a enzima 3β- hidroxi desydrogenase/Δ5-Δ4-isomerase de esteróides tipo 2 (gene HSD3B2) é responsável pela degradação do DHT, além de contribuir para síntese indireta de testosterona por uma via anabólica. Isto exposto, cenários distintos se apresentam considerando as atividades deficientes dessas enzimas: i) a deficiência congênita da enzima 5a-redutase tipo 2 conduz a uma forma específica de pseudohermafroditismo masculino (PHM) no qual a conversão de T em DHT está nula ou defeituosa, inviabilizando a virilização normal da genitália externa em indivíduos com cariótipo 46,XY e ii) em razão das propriedades bifuncionais da enzima 3β-HSD2, tanto na via de síntese quanto de degradação de andrógenos, sua deficiência congênita pode conduzir a quadros clínicos distintos de ambigüidade genital. No adulto, mutações somáticas que afetem sua atividade enzimática podem contribuir para a manifestação do câncer de próstata, pelo acúmulo do DHT. O presente trabalho aborda as duas enzimas esteroidogênicas envolvidas com o metabolismo da DHT, buscando caracterizar mutações germinativas e/ou somáticas que conduzem a deficiências enzimáticas relacionadas a diferentes condições clínicas. Com relação à deficiência em 5a-redutase tipo 2, investigou-se a presença de mutações germinativas no gene SRD5A2 em amostras de DNA 20 pacientes de sexo genético masculino com suspeita de deficiência em 5α-redutase tipo 2, pertencentes a 18 famílias brasileiras, por meio de sequenciamento direto dos produtos de PCR dos cinco exons do gene e de suas regiões flanqueadoras. Foram identificadas alterações moleculares em 18 desses pacientes, compreendendo tanto mutações não anteriormente referidas na literatura (G158R, del642T, 217_218insC e IVS3+1G>A), como mutações recorrentes já descritas em outros grupos étnicos ou em indivíduos de outras regiões geográficas. Os resultados detalhados, bem como a discussão, acham-se apresentados no Capítulo III.1, sob a forma de artigo publicado. (...continua) / Abstract: The androgenic hormone dihydrotestosterone (DHT) has fundamental relevance in normal male sexual differentiation and in prostate development and maintenance. Two enzymes act directly on the regulation of DHT concentration at cellular level: 1) with an anabolic function the steroid 5α-reductase type 2 enzyme (SRD5A2 gene) leads to DHT synthesis by converting testosterone (T) in 5α-dihydrotestosterone and 2) with a catabolic pathway the 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 enzyme (HSD3B2 gene) is responsible for DHT degradation, besides contributing to indirect synthesis of testosterone in an anabolic pathway. Thus, different scenarios can be considered regarding the deficiencies in the activities of these enzymes: i) congenital steroid 5α-reductase type 2 enzyme deficiency leads to a specific form of male pseudohermaphroditism (MPH), where the conversion of T into DHT is defective or inexistent, preventing normal virilization of the external genitalia in individuals with a 46,XY karyotype; and ii) due to the bi-functional properties of the 3β-HSD2 enzyme, either at synthetic or degradation androgen pathways, its congenital deficiency can lead to distinct manifestations of genital ambiguity. Furthermore, in the adult, somatic mutations that affect 3β-HSD2 enzymatic activities could contribute to prostate cancer manifestation, due to DHT accumulation. The present work approaches these two steroidogenic enzymes involved with the DHT metabolism, aiming to characterize germinal and/or somatic mutations leading to enzymatic deficiencies related to different clinical conditions. Concerning the steroid 5α- reductase type 2 deficiency, we screened for germinal mutations on SRD5A2 gene in DNA samples of 20 patients from 18 Brazilian families with suspected SRD5A2 deficiency, by directly sequencing of the PCR products from the five exons and flanking regions of the gene. Molecular alterations were detected in 18 of these patients, comprising either mutations not previously reported in the literature (G158R, del642T, 217_218insC e IVS3+1G>A) as well as recurring mutations already described in other ethnical groups or in individuals from other geographical regions. The detailed results and corresponding discussion are presented at Chapter III.1, as a published paper. (¿to be continued) / Doutorado / Genetica Animal e Evolução / Doutor em Genetica e Biologia Molecular

(AJ) The three aims of the work were as follows: 1. Comparison of prostate magnetic resonance (MR) examination results from 1.5 T and 3 T scanners in patients with prostate carcinoma (PCa). MR findings of 103 patients (ages 44-72 years) were compared with histopathological results after radical prostatectomy. The work was focused on the accuracy of predicting local cancer staging and determining prostate tumour location. Patients were divided into three groups (A, B and C) based on the type of MR scanner and protocol used. Patient groups A and B were examined in 1.5T and 3T MR scanners equipped with surface coils in the identical multiparametric MR imaging protocol included dynamic contrast examination (DCE). Patient group C was examined in a 3T MR scanner without DCE. The highest accuracy of predicting the stage of PCa was seen in patients examined in 3 T MR scanner with DCE included in the protocol, however, no significant differences were seen between results from 1.5 T and 3.T MR scanners. No significant difference was also found in the accuracy of determining the location of prostate tumour between 1.5 T and 3T MR examinations, however, there were significant differences between sequences used, with the highest accuracy attained by using a combination of T2 weighted sequences and diffusion...

Im Fokus der Dissertation stand die Evaluierung molekularer Möglichkeiten zur Findung geeigneter Biomarker für das Prostatakarzinom (PCa). Zunächst wurde die epigenetische Promotormethylierung der Gene GSTP1, RARbeta2, APC und PITX2 im Hinblick eines möglichen Methylierungsfeldeffektes untersucht. Die RARβ2-Promotormethylierung konnte als potentieller Marker zur Tumorvorhersage im histologisch normal erscheinenden Gewebe bestimmt werden. GSTP1 zeigte eine äußerst spezifische Tumormethylierung, was dessen diagnostisches Potenzial unterstreicht. Die Methylierung korrelierte zudem mit pathologischen Parametern. Ein Screening im Array-Format identifizierte weitere Gene, deren Promotormethylierung diagnostisch interessant sein könnten. Des Weiteren wurden Genexpressionsanalysen angiogenetischer und Endothel-assoziierter Faktoren durchgeführt, deren diagnostische und prognostische Aussagekraft für das PCa ermittelt wurden. Dabei konnte für Caveolin-1 (CAV1) eine signifikante Herunterregulierung der mRNA-Menge im Tumor gezeigt werden. Die Bisulfit-Sequenzierung von sieben CpG-Dinukleotiden im CAV1-Promotor ergab zwischen Tumor- und tumorangrenzendem Gewebe differenzielle Methylierungsmuster, die zu einer verminderten CAV1-Transkription führen könnten. Zudem führte eine 5-Aza-2-desoxycytidin-Behandlung der CAV1-defizienten LNCaP-Zelllinie zur Reexpression. Weiterhin assoziierte CAV1 invers mit pathologischen Parametern und zeigte prognostische und diagnostische Relevanz. Immunhistologisch wurde CAV1 z.T. deutlich verringert in Endothelzellen und Fibroblasten des Tumors nachgewiesen. Ko-Kultivierungsversuche von HUVEC mit konditionierten Zellmedien ergaben z.T. signifikant reduzierte CAV1-Mengen in HUVEC. Die Ergebnisse zeigen, dass epigenetische Veränderungen wertvolle Informationen zur Diagnostik, Prognostik und Progression des PCa liefern. Zudem konnte CAV1 als potentieller Marker des PCa identifiziert werden. / The focus of the thesis was to evaluate molecular possibilities to find suitable biomarkers for prostate cancer (PCa). First, the epigenetic promoter methylation patterns of several genes (GSTP1, RARbeta2, APC and PITX2, respectively) were investigated for a possible methylation field effect. The RARbeta2 promoter methylation could be determined as a possible marker for tumor prediction in histologically normal-appearing tissue. GSTP1 showed a highly specific tumor methylation, underlining its diagnostic potential. The methylation also correlated with pathological parameters. Screening in an array format identified other genes whose promoter hypermethylation could be diagnostically interesting. Furthermore, gene expression analysis of angiogenic and endothelial-associated factors was performed to determine their diagnostic and prognostic potentials for PCa. For CAV1, a significant down-regulation of its mRNA level could be determined in the tumor. Bisulfite sequencing of seven CpG dinucleotides in the CAV1 promoter showed different methylation patterns between tumor and tumor adjacent tissue that could cause a reduced transcription. Furthermore, treatment of the CAV1-deficient LNCaP cell line with 5-aza-2-deoxycytidine led to CAV1 reexpression. Additionally, CAV1 inversely associated with pathological parameters and showed prognostic and diagnostic relevance. Immunohistochemical analysis clearly demonstrated decreases in CAV1 protein expression in endothelial cells and fibroblasts of the tumor. Conditioned media of cultivated tumor cells partly induced downregulation of the CAV1 protein level in HUVEC. The results show that epigenetic and angiogenic processes play crucial roles and provide valuable information for diagnosis, prognosis and progression of PCa. Moreover, CAV1 could be identified as a potential marker of prostate cancer.

Introdução e Objetivo: A invasão de nervos pelo carcinoma da próstata, em biópsias por agulha, pode ser um preditor independente de extensão extra-prostática e pode influenciar no manejo cirúrgico. Nervos são, algumas vezes, difíceis de serem visualizados em biópsias por agulha da próstata coradas pela técnica da hematoxilina e eosina. É possível que, utilizando-se a técnica da imuno-histoquímica com o anticorpo para a proteína S-100, os nervos e a invasão de nervos sejam mais facilmente detectados, reduzindo-se a quantidade de falso-negativos. Material e Método: Foram examinados 101 exames de biópsias por agulha, correspondendo a setenta pacientes, com carcinoma da próstata, através de lâminas coradas pela técnica da hematoxilina e eosina, selecionados a partir de 500 exames consecutivos. Obtiveram-se novos cortes dos mesmos blocos de parafina que foram corados pela técnica imuno-histoquímica, utilizando o anticorpo policlonal para a proteína S-100. O número total de nervos, o número de nervos invadidos pelo carcinoma da próstata, o número de nervos por área de tecido, o número de nervos invadidos por área de carcinoma e o diâmetro dos nervos invadidos pelo carcinoma foram determinados por dois investigadores, nas duas técnicas de coloração. Resultados: Dos 70 pacientes avaliados 31 (44,3%) apresentaram invasão de nervo pelo carcinoma no HE e 43 (61,4%) apresentaram invasão de nervo com a técnica imunohistoquímica da proteína S-100 (p<0,001). Na área de carcinoma foram detectados mais nervos invadidos no S-100 do que no HE (p<0,001). O diâmetro do menor nervo invadido pelo carcinoma foi menor no S-100 do que no HE (p=0,007). Conclusão: A coloração com a técnica imuno-histoquímica com o anticorpo para a proteína S-100 aumenta a sensibilidade para reconhecer nervos em material de punção-biópsia da próstata por agulha. Também, com o S-100 se reconhecem mais invasões de nervos pelo carcinoma da próstata, as quais não eram visualizadas quando coradas com o HE. Desta forma reduziu-se a quantidade de casos falso-negativos e demonstrou-se que o exame criterioso de espécimes corados com o HE não é suficiente para detectar todas as invasões de nervos pelo carcinoma da próstata. / Background: The identification of perineural invasion in prostate needle biopsies may be an independent predictor of extraprostatic extension of prostatic carcinoma and may also affect surgical management. Nerves are often difficult to recognize on hematoxylin and eosin stained prostate needle biopsies. Perhaps using an immunohistochemical stain for S-100 protein, nerves and the presence of perineural invasion, may be more easily detected. Methods: We examined 101 (70 patients) cases of prostatic carcinoma by routine HE stain to determine perineural invasion and nerves. Step sections were immunostained for S- 100 protein (polyclonal antibody). The total nunmber of nerves, the number of nerves showing perineural invasion, the number of nerves per square millimeter of tissue, the number of nerves showing perineural invasion per square millimeter of prostatic carcinoma and the diameter of perineural invasion were determined by two investigators on the HE and S-100 stained prostate needle biopsies. Results: Among the 70 patients, perineural invasion was detected in 31 (44,3%) patients on HE stained sections and in 43 (61,4%) on S-100 stained sections (p<0,001). The prostate needle biopsies on median showed more perineural invasion on S-100 stained than on HE (P<0,001). The minimum diameter of perineural invasion was smaller on S-100 stained than on HE (p=0,007). Conclusions: S-100 staining increases the sensivity with which nerves are recognized in prostate needle biopsies. More significantly, S-100 staining reveals perineural invasion by prostatic carcinoma that is often unrecognized in HE stained sections. These results support that careful examination of routine HE-stained specimens is not sufficient to detect all important nerve invasion.

Introdução e Objetivo: A invasão de nervos pelo carcinoma da próstata, em biópsias por agulha, pode ser um preditor independente de extensão extra-prostática e pode influenciar no manejo cirúrgico. Nervos são, algumas vezes, difíceis de serem visualizados em biópsias por agulha da próstata coradas pela técnica da hematoxilina e eosina. É possível que, utilizando-se a técnica da imuno-histoquímica com o anticorpo para a proteína S-100, os nervos e a invasão de nervos sejam mais facilmente detectados, reduzindo-se a quantidade de falso-negativos. Material e Método: Foram examinados 101 exames de biópsias por agulha, correspondendo a setenta pacientes, com carcinoma da próstata, através de lâminas coradas pela técnica da hematoxilina e eosina, selecionados a partir de 500 exames consecutivos. Obtiveram-se novos cortes dos mesmos blocos de parafina que foram corados pela técnica imuno-histoquímica, utilizando o anticorpo policlonal para a proteína S-100. O número total de nervos, o número de nervos invadidos pelo carcinoma da próstata, o número de nervos por área de tecido, o número de nervos invadidos por área de carcinoma e o diâmetro dos nervos invadidos pelo carcinoma foram determinados por dois investigadores, nas duas técnicas de coloração. Resultados: Dos 70 pacientes avaliados 31 (44,3%) apresentaram invasão de nervo pelo carcinoma no HE e 43 (61,4%) apresentaram invasão de nervo com a técnica imunohistoquímica da proteína S-100 (p<0,001). Na área de carcinoma foram detectados mais nervos invadidos no S-100 do que no HE (p<0,001). O diâmetro do menor nervo invadido pelo carcinoma foi menor no S-100 do que no HE (p=0,007). Conclusão: A coloração com a técnica imuno-histoquímica com o anticorpo para a proteína S-100 aumenta a sensibilidade para reconhecer nervos em material de punção-biópsia da próstata por agulha. Também, com o S-100 se reconhecem mais invasões de nervos pelo carcinoma da próstata, as quais não eram visualizadas quando coradas com o HE. Desta forma reduziu-se a quantidade de casos falso-negativos e demonstrou-se que o exame criterioso de espécimes corados com o HE não é suficiente para detectar todas as invasões de nervos pelo carcinoma da próstata. / Background: The identification of perineural invasion in prostate needle biopsies may be an independent predictor of extraprostatic extension of prostatic carcinoma and may also affect surgical management. Nerves are often difficult to recognize on hematoxylin and eosin stained prostate needle biopsies. Perhaps using an immunohistochemical stain for S-100 protein, nerves and the presence of perineural invasion, may be more easily detected. Methods: We examined 101 (70 patients) cases of prostatic carcinoma by routine HE stain to determine perineural invasion and nerves. Step sections were immunostained for S- 100 protein (polyclonal antibody). The total nunmber of nerves, the number of nerves showing perineural invasion, the number of nerves per square millimeter of tissue, the number of nerves showing perineural invasion per square millimeter of prostatic carcinoma and the diameter of perineural invasion were determined by two investigators on the HE and S-100 stained prostate needle biopsies. Results: Among the 70 patients, perineural invasion was detected in 31 (44,3%) patients on HE stained sections and in 43 (61,4%) on S-100 stained sections (p<0,001). The prostate needle biopsies on median showed more perineural invasion on S-100 stained than on HE (P<0,001). The minimum diameter of perineural invasion was smaller on S-100 stained than on HE (p=0,007). Conclusions: S-100 staining increases the sensivity with which nerves are recognized in prostate needle biopsies. More significantly, S-100 staining reveals perineural invasion by prostatic carcinoma that is often unrecognized in HE stained sections. These results support that careful examination of routine HE-stained specimens is not sufficient to detect all important nerve invasion.

Introdução e Objetivo: A invasão de nervos pelo carcinoma da próstata, em biópsias por agulha, pode ser um preditor independente de extensão extra-prostática e pode influenciar no manejo cirúrgico. Nervos são, algumas vezes, difíceis de serem visualizados em biópsias por agulha da próstata coradas pela técnica da hematoxilina e eosina. É possível que, utilizando-se a técnica da imuno-histoquímica com o anticorpo para a proteína S-100, os nervos e a invasão de nervos sejam mais facilmente detectados, reduzindo-se a quantidade de falso-negativos. Material e Método: Foram examinados 101 exames de biópsias por agulha, correspondendo a setenta pacientes, com carcinoma da próstata, através de lâminas coradas pela técnica da hematoxilina e eosina, selecionados a partir de 500 exames consecutivos. Obtiveram-se novos cortes dos mesmos blocos de parafina que foram corados pela técnica imuno-histoquímica, utilizando o anticorpo policlonal para a proteína S-100. O número total de nervos, o número de nervos invadidos pelo carcinoma da próstata, o número de nervos por área de tecido, o número de nervos invadidos por área de carcinoma e o diâmetro dos nervos invadidos pelo carcinoma foram determinados por dois investigadores, nas duas técnicas de coloração. Resultados: Dos 70 pacientes avaliados 31 (44,3%) apresentaram invasão de nervo pelo carcinoma no HE e 43 (61,4%) apresentaram invasão de nervo com a técnica imunohistoquímica da proteína S-100 (p<0,001). Na área de carcinoma foram detectados mais nervos invadidos no S-100 do que no HE (p<0,001). O diâmetro do menor nervo invadido pelo carcinoma foi menor no S-100 do que no HE (p=0,007). Conclusão: A coloração com a técnica imuno-histoquímica com o anticorpo para a proteína S-100 aumenta a sensibilidade para reconhecer nervos em material de punção-biópsia da próstata por agulha. Também, com o S-100 se reconhecem mais invasões de nervos pelo carcinoma da próstata, as quais não eram visualizadas quando coradas com o HE. Desta forma reduziu-se a quantidade de casos falso-negativos e demonstrou-se que o exame criterioso de espécimes corados com o HE não é suficiente para detectar todas as invasões de nervos pelo carcinoma da próstata. / Background: The identification of perineural invasion in prostate needle biopsies may be an independent predictor of extraprostatic extension of prostatic carcinoma and may also affect surgical management. Nerves are often difficult to recognize on hematoxylin and eosin stained prostate needle biopsies. Perhaps using an immunohistochemical stain for S-100 protein, nerves and the presence of perineural invasion, may be more easily detected. Methods: We examined 101 (70 patients) cases of prostatic carcinoma by routine HE stain to determine perineural invasion and nerves. Step sections were immunostained for S- 100 protein (polyclonal antibody). The total nunmber of nerves, the number of nerves showing perineural invasion, the number of nerves per square millimeter of tissue, the number of nerves showing perineural invasion per square millimeter of prostatic carcinoma and the diameter of perineural invasion were determined by two investigators on the HE and S-100 stained prostate needle biopsies. Results: Among the 70 patients, perineural invasion was detected in 31 (44,3%) patients on HE stained sections and in 43 (61,4%) on S-100 stained sections (p<0,001). The prostate needle biopsies on median showed more perineural invasion on S-100 stained than on HE (P<0,001). The minimum diameter of perineural invasion was smaller on S-100 stained than on HE (p=0,007). Conclusions: S-100 staining increases the sensivity with which nerves are recognized in prostate needle biopsies. More significantly, S-100 staining reveals perineural invasion by prostatic carcinoma that is often unrecognized in HE stained sections. These results support that careful examination of routine HE-stained specimens is not sufficient to detect all important nerve invasion.