Abstract 1 – A Geographic Information System for Evaluating Residential Pesticide Exposure and Prostate Cancer Incidence Agricultural pesticide exposure is hypothesized to be a risk factor for prostate cancer, and such exposures are of particular concern for men living in farming communities where large-scale pesticide applications occur. Prostate cancer incidence data were obtained from the State Health Registry of Iowa for the years 1996 through 2006, and county and census tract level age-adjusted incidence rates were calculated. Historical crop-specific land use records and pesticide sales data for the state of Iowa during 1990 were integrated into a geographic information system (GIS), where estimates of predicted exposure to the four most commonly used pesticides in Iowa (atrazine, metolachlor, cyanazine, alachlor) were produced. Ecological correlation between pesticide exposure and prostate cancer incidence was evaluated using Spearman’s (rank) correlation coefficient and linear regression analysis. Statistically significant associations between prostate cancer incidence and percent of acres of corn and soybean crops were found at both the county (r=0.22, p=.031 and r=0.33, p=.001, respectively) and census tract (r=0.10, p=.007 and r=0.13, p<.001, respectively) level. The associations between percent of land exposed to the specific pesticides and prostate cancer were not statistically significant. Our findings suggest that residential proximity to corn and soybean fields, and by association the pesticides used on those crops, is correlated with increased prostate cancer risk, but that the increase in risk is not correlated with exposure to the four most commonly used pesticides in Iowa in 1990. Findings from this study underscore the need for continued investigation of the association between agricultural exposures and prostate cancer incidence. Abstract 2 – Spatial Analysis of Prostate Cancer Incidence and Residential Pesticide Exposure in Iowa A statistically significant positive association between prostate cancer incidence and residential proximity to corn and soybean fields in Iowa exists. Research suggests that exposure to pesticides used on these crops increases prostate cancer risk. The objective of this study was to investigate clustering of prostate cancer risk in the presence of potential exposure to pesticides in Iowa. Prostate cancer incidence data (1996-2006) were obtained from the State Health Registry of Iowa. Using SaTScan software, clusters of high and low prostate cancer risk were identified. Ecological correlation between exposure to the four most commonly used pesticides (atrazine, metolachlor, cyanazine, alachlor) in Iowa during 1990 and residence in a cluster of relatively high or low prostate cancer incidence was evaluated using Pearson’s chi-square test statistic and logistic regression analysis. Clusters of increased prostate cancer risk were associated with a greater percentage of land used for all crops of interest (i.e., corn and soybean farming (p <0.001), corn farming (p <0.001), soybean farming (p <0.001)) and low exposure to alachlor (p =0.032) than did clusters with decreased risk of prostate cancer. After adjustment for percent of land used for each crop type, no association between pesticide exposure and prostate cancer risk was observed. Residence in or near agricultural communities increases prostate cancer risk. Our findings suggest that residential proximity to exposures specific to corn and soybean farming increases prostate cancer risk. Evaluation of exposure to less commonly used pesticides and those used in lower quantities is needed.   Abstract 3 – Multilevel Analysis of Residential Pesticide Exposure and Prostate Cancer Incidence An association between residential exposure to factors specific to corn and soybean farms in Iowa exists. The objectives of this study were to statistically assess spatial autocorrelation in prostate cancer incidence in Iowa and to evaluate the effect of residential exposure to the most commonly used pesticides for corn and soybean farms in Iowa in 1990 on prostate cancer incidence. Prostate cancer incidence data were obtained from the State Health Registry of Iowa for the years 1996 through 2006. Spatial patterning of age-adjusted incidence rates was assessed via Moran’s I global index of spatial autocorrelation. A hierarchical regression modeling approach with an assumed Poisson distribution was used to characterize the relationship between census tract level prostate cancer incidence and exposure to pesticides. Statistically significant spatial patterning of prostate cancer incidence, corn and soybean fields and pesticide use (p<.001 for all variables) was observed. After adjustment for individual and area level characteristics, prostate cancer risk increased by approximately 25% for each percentage point increase in percent of land used for corn and soybean crops. Prostate cancer risk was approximately 25% higher for Black men exposed to corn and soybean fields compared to white men exposed to corn and soybean fields. Results from this study support the need for further evaluation of residential exposure to environmental hazards specific to corn and soybean farming.

A unique computational approach was undertaken to identify targets of miR-17-3p that impart an oncogenic potential to the cells of the prostate. Utilizing this approach, we identified insulin growth factor receptor 1 (IGF1R) as a potential target of miR-17-3p. IGF1R imparts an oncogenic approach to the cells by helping cells escape apoptosis, become hypertrophic and increase the production of extracellular proteases that allow cells to detach from neighbors. The regulation of insulin growth factor receptor 1 by human microRNA-17-3p was evaluated using a western blot analysis of prostate cancer cell lines. Protein levels were compared in a cell line that expressed a non-targeting control RNA and a cell line that expressed microRNA-17-3p. The cell line that expressed the non-targeting control had significantly higher levels of IGF1R protein than the cell line expressing more of the active microRNA. Based on this experiment, it appears that microRNA-17-3p might regulate the insulin growth factor receptor 1.

Prostate cancer (PCa) cells predominantly metastasize to bone and the complex crosstalk between PCa cells and osteoblasts (bone-forming cells) and osteoclasts (bone-destroying cells) leads to increased tumour growth and worsening of bone disease. Understanding the mechanisms of PCa bone metastasis can identify the aggressive fraction of PCa resulting in earlier intervention. The ability of PCa cells to express bone cell-specific features, termed osteomimicry, could potentially explain the osteotropic nature of PCa cells. The aim of this study was to determine the role of osteomimicry in the regulation of epithelial-mesenchymal transition (EMT) in bone metastatic prostate cancer cells. It was demonstrated that the osteoblast-specific marker alkaline phosphatase (bone/liver/kidney) (ALPL) was overexpressed in bone metastatic (ARCaPM), compared to non-metastatic (ARCaPE), human PCa cells. Knockdown of ALPL resulted in decreased cell viability, increased cell death and a change from mesenchymal to epithelial morphology in ARCaPM and PC3 cells, and increased CDH1 expression along with decreased migration in ARCaPM cells. Treatment with extracellular ATP also resulted in decreased viability, increased expression of epithelial markers (CDH1, KRT14) and decreased expression of mesenchymal markers (VIM, ZEB1), and reduced expression of ALPL in ARCaPM cells. Small RNA-sequencing identified microRNAs differentially expressed between ARCaPE and ARCaPM PCa cell lines: miR-373 expression was lower in ARCaPM compared to ARCaPE cells and its overexpression in ARCaPM cells resulted in a change to epithelial morphology, increased expression of the epithelial marker CDH1 and decreased expression of the mesenchymal markers VIM and ZEB1. Finally, the development of a high-throughput screening method to identify novel microRNA regulators of osteomimicry was described, which identified two microRNAs miR-199a-5p and miR-212 as positive regulators of ALP activity. Taken together, this thesis describes the identification of ALPL and ATP as novel regulators of epithelial-mesenchymal transition in PCa cells and high-throughput ALP-activity screening as a powerful tool to identify novel microRNA regulators of ALP expression.

An instrument is being developed at the Department of Biomedical Engineering; Research and Development (MT-FoU), at the University Hospital of Umeå with the aim to detect prostate cancer ex vivo. Using a combination of tactile resonance technology and Raman spectroscopy the instrument is intended to be used in the operating room during radical prostatectomy to identify positive surgical margins. The hypothesis was that the length of the piezoelectric element used in the tactile resonance sensor affects the sensor's sensitivity and reproducibility when measuring the stiffness of soft tissue, and that there might be an optimal impression depth to measure at. The specific aim of this study was to evaluate two piezoelectric elements, of different lengths, by the sensitivity and reproducibility of the measurements they performed. Measurements were performed on five silicone samples of different stiffness, during a 2 mm impression. The standard deviation of the stiffness parameters, the R2 of the linear regression used to determine the stiffness parameter, and the depth at the which the most linear relationship between impression force and frequency shift was found were studied using linear mixed-effects models to identify any significant differences between the elements. The long element had a significantly higher R2 of 0.98 compared to 0.93 for the short element, and a higher measurement depth of 0.47 mm compared to 0.37 mm for the short element. No difference between the elements were found on accuracy as measured by standard deviation of the stiffness parameter. It was concluded that this was not enough to claim that one element was better than the other. / Ett instrument utvecklas på avdelningen för Medicinsk teknik, forskning och utveckling, vid Norrlands universitetssjukhus med målet att detektera prostatacancer ex vivo. Instrumentet kombinerar taktil resonansteknologi med Ramanspektroskopi och är tänkt att användas i operationssalen under radikal prostatektomi för att identifiera positiv kirurgisk marginal. Hypotesen var att längden av det piezoleketriska element som används i den taktila resonanssensorn påverkar sensorns känslighet och reproducerbarhet vid mätning av styvhet av mjukvävnad, och att det kan finnas ett optimalt intryckningsdjup att mäta på. Målet med denna studie var att utvärdera två piezoelektriska element, av olika längd, utifrån känsligheten och reproducerbarheten av mätningarna de utförde. Mätningarna gjordes på fem silikonsprover av olika styvhet, under 2 mm intryckning. Standardavvikelsen av styvhetsparametern, R2 av den linjära regression som användes för att bestämma styvhetsparametern, samt det intryckningsdjup på vilket det mest linjära förhållandet mellan intryckningskraft och frekvensskift hittades, studerade med så kallade linear mixed-effects modeller för att identifiera signifikanta skillnader mellan elementen. Det långa elementet hade ett signifikant högre R2 på 0.98 jämfört med det korta elementets 0.93, och ett högre mätdjup på 0.47 mm jämfört med det korta elementets 0.37 mm. Ingen skillnad mellan elementens standardavvikelser av styvhetsparametern hittades. Slutsatsen drogs att resultatet inte var nog för att påstå att det ena elementet är bättre än det andra.

De nombreuses données expérimentales et cliniques ont montré l'importance des cellules Natural Killer (NK) dans l'immunosurveillance antitumorale. Les stratégies thérapeutiques basées sur les cellules NK pourraient donc être une alternative de choix dans le traitement de certains types de cancers. Nous avons focalisé notre étude sur deux types de cancer incurables malgré les récents progrès thérapeutiques : la leucémie lymphoïde chronique B (LLC-B) et le cancer de la prostate. Le but de notre étude est une meilleure compréhension des mécanismes mis en place par les cellules B leucémiques et les cellules tumorales prostatiques pour échapper à la réponse antitumorale des cellules NK. La connaissance de ces mécanismes d'échappement est un pré-requis indispensable à l'utilisation des cellules NK dans les thérapies antitumorales. Concernant la LLC-B, nos résultats suggèrent que les cellules NK de patients, fonctionnellement compétentes, ne peuvent pas initier une réaction immunitaire appropriée envers les cellules B leucémiques due au manque de reconnaissance de ces dernières. Concernant le cancer de la prostate, nos données préliminaires montrent que les cellules NK circulantes de patients sont également fonctionnellement compétentes, quelque soit le stade de la maladie, malgré la diminution significative de l'expression du récepteur NKp30. Ainsi, le degré d’immunogénicité des cellules B leucémiques et celui des cellules tumorales prostatiques devra être autant pris en compte que la fonctionnalité des cellules NK dans les stratégies visant à optimiser l'activité antitumorale de ces dernières. / Many experimental and clinical data have enlightened the importance of Natural Killer (NK) cells in tumor immunosurveillance. Therapeutic strategies based on NK cells could be an alternative in the treatment of certain cancers. We focused our study on two types of incurable cancers despite recent advances in treatment: B chronic lymphocytic leukemia (B-CLL) and prostate cancer. The aim of our study is a better understanding of the mechanisms set up by leukemic B cells and prostate cancer cells to escape from NK antitumor response. The knowledge of these escape mechanisms is an essential prerequisite to the use of NK cells in antitumor therapies. Regarding B-CLL, our results suggest that NK cells, although functionally competent, can not initiate an appropriate immune response against leukemic B cells due to a lack of recognition of the latter. Concerning the prostate cancer, our preliminary data show that circulating NK cells are functionally competent, whatever the stage of disease, despite the significant decrease in expression of the receptor NKp30. Thus, the degree of immunogenicity of leukemic B cells and of the prostate cancer cells must be taken into account as well as the functionality of NK cells in strategies aiming at improving NK antitumor activity.

Le tissu adipeux périprostatique (TAPP) est potentiellement impliqué dans l’agressivité du cancer de la prostate (CaP). Nous avons identifié une association négative entre un taux élevé d’acide linoléique (AL) et d’acide eicosapentaénoïque (EPA) dans le TAPP, l’agressivité de la maladie et la migration des cellules cancéreuses in vitro. La migration des cellules tumorales est liée au phénomène de transition épithélio-mésenchymateuse (TEM), induit par des facteurs du microenvironnement, dont le TGFb et l’hypoxie. Nous avons démontré dans le CaP la signification clinique de la TEM et son facteur de transcription clé Zeb1, dont l’expression augmente lors de la progression du cancer avec un impact sur la survie. Nous avons ensuite montré que l’incorporation de l’AL et de l’EPA dans la membrane plasmique des cellules cancéreuses prostatiques inhibe la migration cellulaire et l’expression de Zeb1 induite par le TGFb et l’hypoxie, in vitro et ex vivo. Nous avons également démontré que l’expression de Zeb1 est dépendante d’une entrée SOCE, impliquant le canal SK3, et régulée par l’AL et l’EPA. Cette régulation de l’entrée calcique par l’AL et l’EPA a également été observée ex vivo dans des explants de CaP humains. / Periprostatic adipose tissue (PPAT) has been suggested to be involved in the modulation of prostate cancer (PCa) progression. We demonstrated herein that low contents of linoleic acid (LA) and eicosapentaenoic acid (EPA) in PPAT are associated with PCa aggressiveness and cancer cell migration in vitro. Cell migration is linked to the process of epithelial-mesenchymal transition (EMT), induced by microenvironmental factors, such as TGFb and hypoxia. We demonstrated in PCa the clinical value of EMT and its key transcription factor Zeb1, which expression increases with the stages of PCa progression, with an impact on survival. Then we have shown, in vitro and ex vivo, that the incorporation of LA and EPA into the plasma membrane of PCa cells inhibits TGFb- and hypoxia-induced cell migration and Zeb1 expression. We also demonstrated that Zeb1 expression is dependent on SOCE influx, involving SK3 channel, and regulated by LA and EPA. This regulation of calcium entry by LA and EPA has also been observed ex vivo in human PCa slices.

Given a global online sample of Black men (n=194) who responded to a social media campaign and completed the study, the convenience sample of Black males (N=194) was mostly married (N=147, 75.85%), had a mean age of 49.53 years (min 40, max 76, SD=8.73), and was well educated; 24.7% (n=48) had an Associate Degree, 20.6% (n=40) had a Bachelor’s, 18% (n=35) had a Master’s, and 5.2% (n=10) had a Doctorate. The mean annual income was 4.21 for category 4 of $40,000-$49,999 (min 1, max 9, SD=1.64). Most of the participants were employed (n=188, 96.9%) and born in the United States (n=152, 78.4%). As a reflection of a global sample, if not a sample of men born in Ghana (77.3%, n=194) who were now dispersed across the globe, over two-thirds (77.3%) were born in Ghana while 78.4% (n=152) were currently living in the United States; 15.5% (n=30) were currently living in Ghana, followed by 5.1 (n=10) currently living in other countries. Key findings showed that, as a brief intervention of taking the PC-S-KT-39, as per results of four paired t-tests (Bonferroni Adjustment Significance, .05/4, p=.013), this was associated with a significant increase from pre-knowledge test to post-knowledge test (p<.000; Bonferroni Adjustment Significance, .05/4, p=.013) for (a) knowledge of prostate cancer and screening (t=-8.475, df=193, p=.000); (b) self-efficacy for talking to doctor about prostate cancer and screening (t=-9.098, df=193, p=.000); (c) knowledge of Vitamin D screening and supplementation (t=-9.748, df=193, p=.000); and (d) self-efficacy for talking about Vitamin D screening and supplementation (t=-9.384, df=193, p=.000). The study demonstrated how there is great value in contemporary times in using an online social media campaign, posting and distributing flyers in community venues (barber shops, churches), snowballing, and using smart phones to conduct global online research. Given these findings, wide dissemination via the Internet of a link to the new Prostate Cancer and Screening Knowledge Test (PC-S-KT-39) is justified. If men such as those in this study disseminate the link, the impact may be global indeed.

Modelos experimentais de câncer de próstata demonstraram níveis aumentados de protoporfirina IX (PpIX) no sangue e nas fezes de camundongos, fazendo com que a quantificação dessa molécula pudesse ser aventada para a identificação desse tipo de tumor. Nesse estudo do tipo caso-controle, a autofluorescência de porfirinas em fezes humanas foi analisada usando espectroscopia de fluorescência em pacientes com câncer de próstata e controles. Dados sociodemográficos, amostras sanguíneas para determinação dos níveis de PSA (antígeno prostático específico) e amostras de fezes para quantificação de porfirinas foram obtidas após consentimento dos pacientes. Recrutaram-se 18 pacientes em amostra calculada a partir dos estudos de referência. Realizou-se varredura para encontrar o melhor pico espectrofotométrico a partir de diversas diluições acetona/fezes. Primeiramente, 3 mililitros de acetona de grau analítico foram adicionados a 0,3 gramas de fezes e a mistura foi macerada e centrifugada a 4.000 rotações por minuto durante 15 minutos. O sobrenadante foi analisado espectroscopicamente. Os espectros de emissão a 550-750 nm foram obtidos excitando as amostras a 405 nm. Variáveis sociodemográficas foram analisadas e evidenciaram homogeneidade entre os grupos estudados. Um contraste significativo entre as amostras de indivíduos normais e oncológicos foi estabelecido na região espectral de 670-675 nm (p = 0,000127), o que corresponde a um aumento significativo de porfirinas fecais em pacientes com câncer. Não houve correlação estatisticamente significativa entre os níveis de PSA e as porfirinas fecais (R = -0,0221). Neste estudo preliminar realizado em seres humanos, os resultados mostram um método simples e não invasivo para avaliar as porfirinas fecais, que têm o potencial de funcionar como um biomarcador tumoral em pacientes com câncer de próstata. Essa abordagem poderia aumentar a sensibilidade e a especificidade do teste de PSA. / Experimental models of prostate cancer have demonstrated increased levels of protoporphyrin IX (PpIX) in the blood and faeces of mice. Hence, the quantification of these autofluorescent molecules could be hypothesized to be a potential marker for this type of tumour. In this case-control study, the autofluorescence of porphyrins in human faeces from patients with prostate cancer and control subjects was analysed using fluorescence spectroscopy. Socio-demographic data, blood samples for determination of PSA levels and faeces samples for quantification of porphyrins were obtained after consent of the patients. Eighteen patients were recruited in a sample calculated from the reference studies. Scanning was performed to determine the best spectrophotometric peak from various acetone/faecal dilutions. First, 3 mL of analytical-grade acetone was added to 0.3 g of faeces, and the mixture was macerated and centrifuged at 4000 rpm for 15 min. The supernatant was analysed spectroscopically. The emission spectra from 550 to 750 nm were obtained by exciting the samples at 405 nm. Socio-demographic variables were analyzed and showed homogeneity among the groups studied. A significant difference between the samples from control and cancer subjects was established in the spectral region of 670675 nm (p = 0.000127), which corresponds to a significant increase in faecal porphyrins in patients with cancer. There was no statistically significant correlation between PSA levels and faecal porphyrins (R = -0,0221). In this preliminary study conducted in humans, the results show a simple and non-invasive method to assess faecal porphyrins, which have the potential to function as a tumour biomarker in patients with prostate cancer. This approach has improved sensitivity and specificity over PSA testing.

Orientador: Valber de Albuquerque Pedrosa / Resumo: Neste trabalho foram desenvolvidas metodologias para detecção de biomarcadores cancerígenos utilizando sensores aptaméricos. Aptâmeros são estruturas tridimensionais de DNA/RNA capazes de serem seletivos a alvos específicos. O uso destas sequências em plataformas eletroquímicas permite que o monitoramento do metabolismo celular se torne viável de uma forma rápida e exata. Para a caracterização das superfícies foram utilizadas as técnicas eletroquímicas. Foram utilizadas três proteínas biomarcadoras, PSA, fPSA e HK2 como modelos para os estudos. Os limites de detecção do aptasensor para PSA e fPSA obtidos foram de 1,1 ng/mL e 2,9 ng/mL, respectivamente. Ao final dos experimentos com linhagens celulares cancerígenas e controle, as correspondentes corroboraram com a classificação de risco do câncer de próstata bem como a capacidade de diferenciação por parte dos aptasensores entre os tipos celulares mais agressivos (PC-3, [PSA]: 23 ng/mL; [fPSA]: 6 ng/mL) e menos agressivos (LNCaP, [PSA]:12 ng/mL; [fPSA]: 7,8 ng/mL) em comparação aos grupos de referência (PNT-2, [PSA]: 1,95ng/mL; [fPSA]: 2,11 ng/mL). Para a HK2, foi possível detecta-lá na presença de todos os tipos celulares prostáticos de maneira qualitativa. / Mestre

O câncer de próstata (CaP) é o tumor maligno mais frequente e uma das principais causas de morte por câncer na população masculina no mundo e no Brasil. Três fatores são de fundamental importância no prognóstico da doença: o estadiamento, o grau histológico (avaliado pelo escore de Gleason) e o antígeno prostático específico (Prostate Specific Antigen - PSA). Há fatores adicionais descritos que podem influenciar na evolução do câncer, como invasão perineural, invasão angiolinfática, acometimento da cápsula, lateralidade do tumor, estágio tumoral e invasão de linfonodos. Embora a associação entre mutações do BRCA2 e o risco de câncer de próstata esteja bem documentado, pouco se sabe sobre o papel do BRCA2 na progressão do câncer de próstata após o diagnóstico inicial. O presente trabalho se propõe a melhor elucidar o papel da proteína BRCA2 nos carcinomas prostáticos comparando os resultados da expressão proteica de BRCA2 com dados clinicopatológicos de pacientes acometidos por Câncer de Próstata, além de avaliar a expressão de BRCA2 com escore de Gleason >=7 após a prostatectomia, tanto na classificação de Gleason segundo Epstein 2005, quanto na classificação do grau de Gleason definida em 2014 com suas respectivas biópsias por agulha. Dos arquivos do Serviço de Patologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, foram selecionados 125 blocos de parafina com amostras de câncer de próstata diagnosticados entre 2005 e 2010. As lâminas coradas com hematoxilina e eosina (H&E) foram utilizadas para a construção de microarranjos teciduais (TMAs). Nesses TMAs foi realizado estudo imunohistoquímico para BRCA2. A proteína BRCA2 com ponto de corte de 15% (classificação antiga) foi superexpressa em 118 casos (94,4%), enquanto a expressão de BRCA2 com cut-off de 56% (classificação nova) foi expressa em 63 (51,2%) de 125 casos. A superexpressão de BRCA2 associada a classificação antiga de Gleason correlacionou-se com bilateralidade do tumor e com estágio tumoral, em contrapartida a expressão de BRCA2 associada a atual classificação se correlacionou apenas com lesão intraepitelial prostática (PIN). Nossos resultados indicam que a expressão de BRCA2 pode ser um biomarcador importante de progressão tumoral nos carcinomas de próstata. / Prostate cancer (PCa) is the most common malignancy and a major cause of cancer death in male population in the world and in Brazil. Three factors are of fundamental importance in the prognosis of the disease: the staging, histological grade (measured by Gleason score) and the Prostate Specific Antigen (PSA). There are additional factors described that may influence the development of cancer, such as perineural invasion, angiolymphatic invasion, capsule involvement, tumor laterality, tumor stage and lymph node invasion. Although the association between mutations in Breast Cancer Gene 2 (BRCA2) and the risk of prostate cancer is well documented, little is known about the role of BRCA2 in the progression of prostate cancer after initial diagnosis. This study aims to elucidate the role of BRCA2 protein in prostate carcinomas comparing the results of the BRCA2 protein expression with clinicopathological data of patients with prostate cancer. For that reason, we evaluated the expression of BRCA2 with Gleason score >=7 after prostatectomy, both in the second Epstein 2005 Gleason score, and in the classification of Gleason grade set in 2014 with their respective needle biopsies. 125 paraffin blocks with prostate cancer samples diagnosed between 2005 and 2010 were selected from the archives of Hospital Pathology Service of the Ribeirao Preto Medical School, University of Sao Paulo. The slides stained with hematoxylin and eosin (H&E) were used for the construction of the tissue microarrays (TMAs). These TMAs was performed immunohistochemical study for BRCA2. The BRCA2 protein with a cut-off point of 15% (old classification) was overexpressed in 118 cases (94.4%), while the expression of BRCA2 to cut off 56% (new classification) was expressed in 63 (51.2%) of 125 cases. The BRCA2 associated overexpression of the old classification of Gleason presented correlation with tumor bilateralism and tumor stage, however BRCA2 expression associated with the current classification was correlated only with Prostatic Intraepithelial Lesion (PIN). Our results indicate that BRCA2 expression can be an important marker of tumor progression in prostate carcinomas.