Association of high-grade prostatic intraepithelial neoplasia immunohistochemical profile with acinar adenocarcinoma of the prostate.

BACKGROUND: Prostate carcinoma is the second leading cause of cancer and the fifth cause of cancer death in men worldwide. OBJECTIVE: To know high-grade prostatic intraepithelial neoplasia and prostate acinar adenocarcinoma immunohistochemical profiles. MATERIAL AND METHODS: Observational, analytical, cross-sectional, retrospective study of specimens obtained by cutting needle biopsy and prostate resection from subjects diagnosed with acinar adenocarcinoma of the prostate and high-grade prostatic intraepithelial neoplasia between January 2015 and December 2020. Tissue microarrays were performed and, subsequently, immunohistochemical studies for BCL2, EGFR, p53, Her2/neu and Ki67. Descriptive statistics were used to analyze clinicopathological factors. Qualitative variables were compared with Fisher's exact test. RESULTS: Twenty-three patients were studied; eight (34%) with angiolymphatic invasion, 14 (60.8%) with perineural invasion, five (21.2%) with prostatitis, and four (17.3%) with fibroadenomatous hyperplasia. HER2/neu (p = 0.1023), p53 (p = 1) and BCL2 expression (p = 0.4136) was observed. CONCLUSION: HER2/neu increased expression was identified in high-grade prostatic intraepithelial neoplasia and acinar adenocarcinoma of the prostate.

ANTECEDENTES: En el mundo, el carcinoma de próstata constituye la segunda causa de cáncer y la quinta causa de muerte por cáncer en hombres. OBJETIVO: Conocer el perfil inmunohistoquímico de la neoplasia intraepitelial prostática de alto grado y del adenocarcinoma acinar de próstata. MATERIAL Y MÉTODOS: Estudio observacional, analítico, transversal y retrospectivo de especímenes obtenidos por biopsia con aguja cortante y resección de próstata debido a diagnóstico de adenocarcinoma acinar de próstata y neoplasia intraepitelial de alto grado, entre enero de 2015 y diciembre de 2020. Se realizaron microarreglos tisulares y, posteriormente, estudios de inmunohistoquímica para BCL2, EGFR, p53, Her2/neu y Ki67. Se realizó estadística descriptiva para analizar los factores clinicopatológicos; las variables cualitativas se compararon con prueba exacta de Fisher. RESULTADOS: Se estudiaron 23 pacientes, ocho (34 %) con invasión angiolinfática, 14 (60.8 %) con invasión perineural, cinco (21.2 %) con prostatitis y cuatro (17.3 %) con hiperplasia fibroadenomatosa. Se observó expresión de HER2/neu (p = 0.1023), p53 (p = 1) y BCL2 (p = 0.4136). CONCLUSIÓN: Se identificó mayor expresión de HER2/neu en la neoplasia intraepitelial prostática de alto grado y el adenocarcinoma acinar de próstata.

High-lipid nutritional environment in different ontogenetic periods induce developmental programming of rat prostate at aging.

In brief: Maternal obesity plus high-fat diet in breastfeeding induces stromal hyperplasia and diffuse acinar atrophy in the rat prostate at aging, related to dyslipidemia and testosterone reduction. The high-lipid nutritional environment from intrauterine and throughout life favors the development of prostatic intraepithelial neoplasia and aggravated degenerative alterations in the gland. Abstract: Maternal obesity and high-fat diet (HFD) affect permanently prostate histophysiology in adulthood, but the consequences during aging are unknown. Here, we evaluated the prostate alterations in middle-aged rats subjected to a high-lipid nutritional environment (HLE) in different ontogenetic periods. Wistar rats (56 weeks of age) were assigned into groups exposed to standard nutrition (C) or HLE during gestation (G), gestation and lactation (GL), from lactation onward (L), from weaning onward (W) and from gestation onward (AL). HLE in the periods after weaning consisted of HFD (20% fat), and during gestation and lactation it also included previous maternal obesity induced by the HFD. HLE increased total cholesterol and triglyceride levels in all groups and led to insulin resistance in GL and AL and obesity in L. Serum testosterone levels decreased ~67% in GL, ~146% in L and W, and ~233% in AL. Histological and stereological analysis revealed an increment of the stromal compartment and collagen fibers in the prostates of all HLE groups, as well as degenerative lesions, such as cell vacuolation and prostate concretions. HLE aggravated acinar atrophy in G, GL, and L, and in AL it reached more than 50% of the prostate area for most animals. The foci of prostatic intraepithelial neoplasia increased in AL. Tissue expression of androgen receptor did not vary among groups, except for a higher stromal expression for G and GL. Even when restricted to gestation and lactation, HLE induces diffuse acinar atrophy in the aging prostate and worsens degenerative and premalignant lesions when it continues throughout life.

Diagnóstico ecográfico de la neoplasia prostática y su relación histológica / Ultrasound diagnosis of prostatic neoplasia and histological relationship

Introducción: El desarrollo de la tecnología con el ultrasonido transrectal ha permitido obtener imágenes diagnósticas de la glándula prostática; su interés deriva de la inmensa frecuencia de problemas clínicos, tanto benignos como malignos. El medio diagnóstico del cáncer de próstata se basa en una biopsia dirigida por ultrasonido transrectal en la mayoría de los casos. Objetivo: Determinar los hallazgos ultrasonográficos y su relación con estudios histopatológico en el diagnóstico de la neoplasia prostática, de los pacientes con sospecha, atendidos en la consulta de urooncología. Métodos: Se realizó un estudio descriptivo transversal en pacientes con sospecha clínica de cáncer prostático, procedentes del servicio de urología en el Hospital Celia Sánchez Manduley en el período comprendido entre julio de 2019 a julio de 2021; que acudieron a consulta con indicación de ultrasonido transrectal. El universo estuvo constituido por 105 pacientes. Se utilizaron criterios de inclusión y exclusión para la selección del universo, previo consentimiento informado de los pacientes. Las variables estudiadas fueron: edad, color de la piel, síntomas clínicos, hallazgos del ultrasonido transrectal, relación ecosonográfica- anatomopatológico. Resultados: Predominó el grupo de edad de 60 a 79 años, de la raza negra, con síntomas urinarios obstructivos bajos, con presencia del nódulo hipoecoico. Predominó la localización ultrasonográfica periférica, así como el adenocarcinoma prostático como hallazgos anatomopatológico encontrado a través de la biopsia. Conclusiones: Se demostró correlación ecográfica-histológica y anatomopatológica(AU)

Introduction: The development of transrectal ultrasound technology has made it possible to obtain diagnostic images of the prostate gland; its interest derives from the massive frequency of clinical problems, both benign and malignant. The diagnosis of prostate cancer is based on a transrectal ultrasound-guided biopsy in most cases. Objective: To determine the ultrasonographic findings and the how they relate with histopathological studies in the diagnosis of prostatic neoplasia in suspected patients treated in the uro-oncology clinic. Methods: A cross-sectional descriptive study was carried out in patients with clinical suspicion of prostate cancer, in the urology service at Celia Sánchez Manduley Hospital from July 2019 to July 2021; they attended the consultation with an indication for transrectal ultrasound. The universe consisted of 105 patients. Inclusion and exclusion criteria were used for the selection of the universe, with the prior informed consent of the patients. The variables studied were age, skin color, clinical symptoms, transrectal ultrasound findings, echosonographic-pathological relationship. Results: Predominance was observed of subjects from the age group of 60 to 79 years, black race, with lower obstructive urinary symptoms, and presence of hypoechoic nodule. Peripheral ultrasonographic location prevailed, as well as prostatic adenocarcinoma as pathological findings found through biopsy. Conclusions: Ultrasound-histological and pathological correlation was demonstrated(AU)

Avaliação de fatores de risco e antígeno prostático específico no rastreamento de câncer de próstata / Evaluation of risk factors and prostate-specific antigen in prostate cancerscreening

Introdução: no Brasil, o câncer de maior incidência nos homens é o câncer de próstata (CaP), com 6,9% de mortalidade. Atualmente, discute-se a aplicabilidade do antígeno prostático específico (PSA) em políticas de rastreamento para CaP e os riscos associados ao sobrediagnóstico. Objetivo: correlacionar a dosagem do PSA com fatores de risco, história clínica e a presença de neoplasia prostática. Metodologia: estudo descritivo transversal que analisou, comparativamente, dados clínico-epidemiológicos e níveis séricos de PSA de 200 pacientes. Valores de PSA foram estratificados em três categorias (<2,5, 2,5­10,0 e >10 ng/ml). Resultados: os fatores de risco analisados foram relacionados significativamente com o aumento do PSA e neoplasia prostática. A prevalência de CaP (11%) e hiperplasia prostática (61%) foi observada nos pacientes com maior dosagem de PSA, enquanto 1% dos pacientes apresentou CaP sem alteração do PSA e 4% tiveram CaP com 2,5­10,0 ng/ml de PSA. Maiores níveis séricos do biomarcador foram relacionados a diabetes (70%), hipertensão (77%), uso crônico de medicações (60%) e ausência de exames periódicos (58%). O grupo com PSA >10 ng/ml teve média de idade maior que o primeiro (p = 0,002) e o segundo grupos (p = 0,027). Conclusão: a prevalência de hiperplasia prostática benigna associada à alteração do PSA, e o elevado risco de exames falso-positivos evidenciam a preocupação com o sobrediagnóstico. No contexto dos dados clinico-epidemiológicos avaliados, a possibilidade de resultados falso-positivos e falso-negativos associados à dosagem do PSA deve ser considerada, ressaltando a importância de adoção de exames complementares para rastreio do CaP.

Introduction: in Brazil, the cancer with the highest incidence in men is prostate cancer (PCa), with 6.9% mortality. Currently, the applicability of prostate specific antigen (PSA) in screening policies for PCa and the risks associated with overdiagnosis are discussed. Objective: to correlate the PSA level with risk factors, clinical history and the presence of prostatic neoplasm. Methods: a cross-sectional descriptive study that analyzed, comparatively, clinical-epidemiological data and serum PSA levels of 200 patients. PSA values were stratified into three categories (<2.5, 2.5­10.0 and> 10 ng / ml). Results: the risk factors analyzed were significantly related to the increase in PSA and prostatic neoplasm. The prevalence of PCa (11%) and prostatic hyperplasia (61%) was observed in patients with higher levels of PSA, while 1% of patients had PCa without PSA changes and 4% had PCa with 2.5­10.0 ng/ml PSA. Increased serum levels of the biomarker were related to diabetes (70%), hypertension (77%), chronic use of medications (60%) and periodic exams (58%). The group with PSA> 10 ng/ml had a mean age greater than the first (p = 0.002) and the second group (p = 0.027). Conclusion: the prevalence of benign prostatic hyperplasia associated with PSA change and an increased risk of false-positive tests show a concern with overdiagnosis. In the context of clinical-epidemiological data, the possibility of false-positive and false-negative results associated with the PSA measurement have to be considered, highlighting the importance of complementary tests for PCa screening.

Incidencia de adenocarcinoma en zona transicional de próstata en institución pública. Cochabamba, Bolivia / Incidence of Adenocarcinoma in Transitional Zone of Prostate in public

El cáncer en la zona de transición representa el 20-25% de los casos (en piezas de prostatectomías radicales), su diagnóstico con frecuencia es de manera incidental, siendo identificados clínicamente como supuestos adenomas. OBJETIVO: determinar la incidencia de Adenocarcinoma en la Zona transicional de Próstata e identificar etapas precancerosas en pacientes con clínica de HPB. MÉTODS: estudio longitudinal de tipo retrospectivo desde el 2013-2018 en la ciudad de Cochabamba-Bolivia; población de estudio: pacientes sometidos a prostatectomía simple, retropúbica y/o transvesical. Recolección de datos: a partir de historias clínicas, en pacientes con clínica de hiperplasia benigna de próstata y PSA total < 4 ng/ml. RESULTADOS: se identificó 76 pacientes, de los cuales; 5 pacientes resultaron con Adenocarcinoma y 9 pacientes con: Neoplasia Intraepitelial Prostática de Alto Grado 2,6 %, Proliferación acinar pequeña atípica 7,9%, representando así un 10,5%. En cuanto a la invasión representaron un 5,3% con invasión perineal, 2,6% invasión linfovascular y ninguno con invasión extravascular. DISCUSIÓN: pacientes con cáncer de próstata zona transicional, presentan un Antígeno prostático específico alto susceptibles a Adenocarcinoma. Sin embargo, en esta investigación se encontró Adenocarcinoma de próstata de alto riesgo con Antígeno prostático específico total menor a 4 ng/ml. A pesar de los instrumentos clínicos e indicaciones para la decisión de terapia quirúrgica de una supuesta hiperplasia prostática benigna, existe en el estudio una incidencia del 6,5% de Adenocarcinoma en Zona Transicional, con un 10,5 % de incidencia de presentación de formas precancerosas y el 17,1% de los pacientes del estudio se encuentran en riesgo de letalidad de la enfermedad.

Cancer in the transition zone represents 20-25% of cases, its diagnosis is often incidental, being identified clinically as suspected adenomas. OBJECTIVE: to determine the incidence of adenocarcinoma in the transitional Prostate Zone and identify the degree of adenocarcinoma and precancerous stages thereof. METHODS: longitudinal retrospective study from 2013-2018 in the city of Cochabamba-Bolivia; Study population: patients undergoing simple, retropubic and / or transvesical prostatectomy. Data collection: from medical records, in patients with benign prostatic hyperplasia and who have no atypia and neoplasms. RESULTS: 76 patients were identified, of which; 5 patients resulted with adenocarcinoma and 9 patients among: High Grade Prostatic Intraepithelial Neoplasia 2.6%, small atypical acinar proliferation 7.9%, thus representing 10.5%. As for the invasion, they represented 5.3% with perineal invasion, 2.6% lymphovascular invasion and none with extravascular invasion. DISCUSSION: Patients with transitional prostate cancer have a high specific prostate antigen susceptible to adenocarcinoma. However, this investigation found high-risk prostate adenocarcinoma with total prostate antigen total less than 4 ng / ml. Despite the clinical instruments and indications for the decision of surgical therapy of an alleged benign prostatic hyperplasia, there is a 6.5% incidence of adenocarcinoma in the Transitional Area, with a 10.5% incidence of presentation of forms of Proliferation of Atypical Small Acini and 17.1% of the patients in the study are at risk of lethality of the disease.

Aluminum exposure promotes histopathological and pro-oxidant damage to the prostate and gonads of male and female adult gerbils.

Since the industrial revolution, all living beings have become susceptible to numerous sources of aluminum (Al) exposure. In addition to causing proven toxicity in many organs and systems, Al can also have estrogenic activity when absorbed by the body. The reproductive organs are commonly affected by environmental pollutants with estrogenic activity, but little is known about the effects of Al on the prostate and gonads. Therefore, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils. After 30 days of oral exposure to aluminum chloride (10 mg/kg/day), the animals were euthanized and the organs processed for cytochemical, ultrastructural, and biochemical assays. Ventral male prostates exposed to Al became hyperplastic and showed signs of cell aging. In addition, the male prostate showed decreased catalase (CAT) and superoxide dismutase (SOD) activity. The female prostate was structurally more affected than the ventral male prostate, since it presented hyperplasia and punctual foci of inflammation and prostatic intraepithelial neoplasia. However, CAT and SOD activities did not change in this gland. In the testis, Al promoted immature germ cell detachment and degeneration, as well as reduced CAT activity. In the ovaries, Al caused reduction in folliculogenesis and decreased SOD activity. Together, these results indicate that Al is toxic to the prostate and gonads of adult gerbils and that continuous exposure to this metal can impair the fertility of individuals of both sexes.

Imunomarcação de TGF-β em próstatas caninas normais e com lesões proliferativas / Immunoexpression of TGF-β in normal canine prostates and with proliferative lesions

O fator de crescimento transformador-β (TGF-β), um mediador do crescimento prostático, induz a angiogênese e inibe a proliferação celular. Neste estudo, esse marcador foi utilizado com o objetivo de avaliar sua imunomarcação no tecido normal e com lesões proliferativas benignas, pré-neoplásicas e neoplásicas da próstata canina. Para isso, foram selecionadas 54 glândulas com histomorfologia normal, hiperplasia prostática benigna (HPB) epitelial, HPB estromal, atrofia inflamatória proliferativa (PIA), neoplasia intraepitelial prostática (PIN) e carcinoma, utilizadas para a confecção de um bloco de microarranjo tecidual (Tissue Microarray - TMA). As lâminas de TMA foram submetidas à técnica de imunoistoquímica com o anticorpo anti-TGF-β, sendo avaliada a intensidade de imunomarcação nas células epiteliais e estromais. Houve imunomarcação de TGF-β no tecido normal e naqueles com lesões proliferativas. Maior imunomarcação de TGF-β foi constatada nas células do tecido prostático normal e com HPB, enquanto as células prostáticas com PIA, PIN e carcinoma exibiram menor imunomarcação dessa citocina, o que sugere a ação do TGF-β na manutenção da homeostase do tecido normal e com lesão proliferativa benigna e na progressão das lesões proliferativas pré-malignas e malignas da próstata canina.(AU)

The transforming growth factor-β (TGF-β), a mediator of prostatic growth induces angiogenesis and inhibits cell proliferation. It was used in this study in order to evaluate its expression in normal prostatic tissue and those with benign proliferative lesions, pre-malignant and malignant prostatic diseases. A total of 54 glands with normal histomorphology, epithelial benign prostatic hyperplasia (BPH), stromal BPH, prostatic inflammatory atrophy (PIA), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma were selected and used in the tissue microarray block (TMA). The TMA slides were subjected to the immunohistochemistry with anti-TGF-β and its staining intensity in epithelial and stromal cells was evaluated. There was TGF-β immunostaining by both normal tissues and those with proliferative lesions. Higher TGF-β immunostaining was observed in cells from normal prostatic tissues and with HPB, whereas prostatic cells with PIA, PIN and carcinoma exhibited lower immunostaining of this cytokine, suggesting the action of TGF-β in the maintenance of normal tissue homeostasis and with benign proliferative lesion and in the progression of pre-malignant and malignant proliferative lesions of the canine prostate.(AU)

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate / Associação entre diminuição da expressão dos receptores de estrógeno alfa e andrógeno, e imunoexpressão de fosfatase e tensina homóloga na próstata canina

Canine prostate gland is a hormonal dependent organ and its imbalance of estrogen and androgen receptor expressions are directly associated with the development of different diseases. Due to the lack of information regarding the behavior of the aforementioned receptors in canine prostate cancer (PC), this study aimed to identify estrogen receptor alpha (ERα), androgen receptor (AR), Ki67 and phosphatase and tensin homolog (PTEN) protein expressions in canine PC by immunohistochemistry. We found nuclear expression of ERα and AR in the epithelial cells of normal canine samples and a loss of protein expression in PC samples. Normal samples showed Ki67 expression in a few basal cells and the PC samples showed the highest mean of positive cells (253.1). Canine prostate cancer showed a high proliferative index, which was associated with independence of hormonal actuation. PTEN showed positive nuclear and cytoplasmic expression in normal canine samples and a loss in PC. Loss of ERα, AR and PTEN indicated that canine PC exhibits the same immunohistochemical phenotype as in human patients with PC resistant to hormonal therapy. Therefore, canine PC should be considered as a model to study human PC resistant to hormonal therapy.(AU)

A glândula prostática canina é um órgão dependente de hormônio, e o desequilíbrio na expressão dos receptores de estrógeno e andrógeno estão diretamente associados com o desenvolvimento de diferentes doenças. Devido à falta de informação sobre o comportamento desses receptores no câncer prostático canino (PC), este estudo tem por objetivo identificar a expressão proteica através da técnica de imuno-histoquímica do receptor de estrógeno alfa (REα), receptor de andrógeno (RA), Ki67 e fosfatase e tensina homóloga (PTEN). Foi encontrado nas células epiteliais prostáticas normais caninas a expressão nuclear de REα e RA, e perda de expressão proteica nas amostras de PC. As amostras normais apresentaram expressão de Ki67 em poucas células basais e as amostras de PC apresentaram a maior média de células positivas (253,1). O câncer de próstata canino apresentou uma taxa alta de proliferação, o qual foi associado com a atuação independente de hormônio. As amostras de próstatas caninas normais revelaram marcação nuclear e citoplasmática da proteína PTEN e perda nas amostras de PC. A perda de REα, RA e PTEN indicam que as amostras de PC exibem o mesmo fenótipo imuno-histoquímico de pacientes humanos com câncer prostático resistente a terapia hormonal. Sendo assim, o PC canino deve ser considerado um modelo para estudos de câncer prostático humano resistente a terapia hormonal.(AU)

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate / Associação entre diminuição da expressão dos receptores de estrógeno alfa e andrógeno, e imunoexpressão de fosfatase e tensina homóloga na próstata canina

Canine prostate gland is a hormonal dependent organ and its imbalance of estrogen and androgen receptor expressions are directly associated with the development of different diseases. Due to the lack of information regarding the behavior of the aforementioned receptors in canine prostate cancer (PC), this study aimed to identify estrogen receptor alpha (ERα), androgen receptor (AR), Ki67 and phosphatase and tensin homolog (PTEN) protein expressions in canine PC by immunohistochemistry. We found nuclear expression of ERα and AR in the epithelial cells of normal canine samples and a loss of protein expression in PC samples. Normal samples showed Ki67 expression in a few basal cells and the PC samples showed the highest mean of positive cells (253.1). Canine prostate cancer showed a high proliferative index, which was associated with independence of hormonal actuation. PTEN showed positive nuclear and cytoplasmic expression in normal canine samples and a loss in PC. Loss of ERα, AR and PTEN indicated that canine PC exhibits the same immunohistochemical phenotype as in human patients with PC resistant to hormonal therapy. Therefore, canine PC should be considered as a model to study human PC resistant to hormonal therapy.(AU)

A glândula prostática canina é um órgão dependente de hormônio, e o desequilíbrio na expressão dos receptores de estrógeno e andrógeno estão diretamente associados com o desenvolvimento de diferentes doenças. Devido à falta de informação sobre o comportamento desses receptores no câncer prostático canino (PC), este estudo tem por objetivo identificar a expressão proteica através da técnica de imuno-histoquímica do receptor de estrógeno alfa (REα), receptor de andrógeno (RA), Ki67 e fosfatase e tensina homóloga (PTEN). Foi encontrado nas células epiteliais prostáticas normais caninas a expressão nuclear de REα e RA, e perda de expressão proteica nas amostras de PC. As amostras normais apresentaram expressão de Ki67 em poucas células basais e as amostras de PC apresentaram a maior média de células positivas (253,1). O câncer de próstata canino apresentou uma taxa alta de proliferação, o qual foi associado com a atuação independente de hormônio. As amostras de próstatas caninas normais revelaram marcação nuclear e citoplasmática da proteína PTEN e perda nas amostras de PC. A perda de REα, RA e PTEN indicam que as amostras de PC exibem o mesmo fenótipo imuno-histoquímico de pacientes humanos com câncer prostático resistente a terapia hormonal. Sendo assim, o PC canino deve ser considerado um modelo para estudos de câncer prostático humano resistente a terapia hormonal.(AU)

Imunomarcação de TGF-β em próstatas caninas normais e com lesões proliferativas / Immunoexpression of TGF-β in normal canine prostates and with proliferative lesions

O fator de crescimento transformador-β (TGF-β), um mediador do crescimento prostático, induz a angiogênese e inibe a proliferação celular. Neste estudo, esse marcador foi utilizado com o objetivo de avaliar sua imunomarcação no tecido normal e com lesões proliferativas benignas, pré-neoplásicas e neoplásicas da próstata canina. Para isso, foram selecionadas 54 glândulas com histomorfologia normal, hiperplasia prostática benigna (HPB) epitelial, HPB estromal, atrofia inflamatória proliferativa (PIA), neoplasia intraepitelial prostática (PIN) e carcinoma, utilizadas para a confecção de um bloco de microarranjo tecidual (Tissue Microarray - TMA). As lâminas de TMA foram submetidas à técnica de imunoistoquímica com o anticorpo anti-TGF-β, sendo avaliada a intensidade de imunomarcação nas células epiteliais e estromais. Houve imunomarcação de TGF-β no tecido normal e naqueles com lesões proliferativas. Maior imunomarcação de TGF-β foi constatada nas células do tecido prostático normal e com HPB, enquanto as células prostáticas com PIA, PIN e carcinoma exibiram menor imunomarcação dessa citocina, o que sugere a ação do TGF-β na manutenção da homeostase do tecido normal e com lesão proliferativa benigna e na progressão das lesões proliferativas pré-malignas e malignas da próstata canina.

The transforming growth factor-β (TGF-β), a mediator of prostatic growth induces angiogenesis and inhibits cell proliferation. It was used in this study in order to evaluate its expression in normal prostatic tissue and those with benign proliferative lesions, pre-malignant and malignant prostatic diseases. A total of 54 glands with normal histomorphology, epithelial benign prostatic hyperplasia (BPH), stromal BPH, prostatic inflammatory atrophy (PIA), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma were selected and used in the tissue microarray block (TMA). The TMA slides were subjected to the immunohistochemistry with anti-TGF-β and its staining intensity in epithelial and stromal cells was evaluated. There was TGF-β immunostaining by both normal tissues and those with proliferative lesions. Higher TGF-β immunostaining was observed in cells from normal prostatic tissues and with HPB, whereas prostatic cells with PIA, PIN and carcinoma exhibited lower immunostaining of this cytokine, suggesting the action of TGF-β in the maintenance of normal tissue homeostasis and with benign proliferative lesion and in the progression of pre-malignant and malignant proliferative lesions of the canine prostate.

Immunoexpression of cell cycle regulators in canine prostate with proliferative lesions / Imunoexpressão de reguladores do ciclo celular em próstatas caninas com alterações proliferativas

Immunostaining of p21, p27, p53, cyclin D1, c-myc was evaluated in normal canine prostate and prostate with proliferative disorders to verify the interaction between these regulators of cell cycle progression. From 106 samples of canine prostate obtained from a TMA block, 15 were considered normal, 16 diagnosed as benign prostatic hyperplasia (BPH), 30 as proliferative inflammatory atrophy (PIA), 20 as prostatic intraepithelial neoplasia (PIN), and 25 as prostatic carcinoma (PC). There was positive correlation between p21 and p27 for number of stained cells and staining intensity in all conditions and between c-myc and p53 in prostates with PIN. Considering the number of labeled cells, there was positive correlation between p21 and p53 in the normal prostate. Relative to the intensity of staining, there was positive correlation between p21 and p53 in prostate tissue with PIN and between p27 and c-myc in prostates with PIA. A negative correlation between c-myc and cyclin D1 was also identified in the glands with PIN, considering the number of labeled cells, and between p27 and c-myc in the prostates with PC for staining intensity. In conclusion, the expression of p21, p27, p53, cyclin D1 and c-myc varies according to type of proliferative lesion in canine prostate. Taken together, the results indicate low growth potential of the canine PC in the presence of p21 and p27 overexpression, cyclin D1 low expression and regular expression of c-myc, even with the expression of p53 mutant type. Further, it was possible reaffirm the premalignant potential of PIA and PIN in canine prostate.(AU)

A imunomarcação de p21, p27, p53, ciclina D1 e c-myc foi avaliada na próstata canina normal e com desordens proliferativas para verificar quanto a interação desses reguladores na progressão do ciclo celular. Um total de 106 amostras de próstata canina foi obtido a partir de um bloco de TMA, sendo 15 normais, 16 hiperplasia prostática benigna (HPB), 30 atrofia inflamatória proliferativa (PIA), 20 neoplasia intraepitelial prostática (PIN), e 25 carcinoma prostático (PC). Foi encontrada diferença na imunomarcação de p21, p27, ciclina D1 e p53 no epitélio acinar em relação aos diagnósticos. Houve correlação positiva entre p21 e p27 para as variáveis número de células marcadas e intensidade de imunomarcação em todos os diagnósticos (normal, HPB, PIA, PIN e PC), e entre c-myc e p53 nas próstatas com PIN. De acordo com o número de células marcadas, houve correlação positiva entre p21 e p53 na próstata normal. De acordo com a intensidade de imunomarcação houve correlação positiva entre p21 e p53 no tecido prostático com PIN e entre p27 e c-myc em próstatas com PIA. Foi observada correlação negativa entre c-myc e ciclina D1 nas glândulas com PIN, considerando o número de células marcadas, e entre p27 e c-myc na próstata com PC, para a variável intensidade de imunomarcação. Conclui-se que a expressão de p21, p27, p53, ciclina D1 e c-myc varia na próstata canina de acordo com o tipo de lesão proliferativa. Em conjunto, os resultados indicam baixo potencial de crescimento dos carcinomas da próstata canina quando há superexpressão de p21 e de p27, baixa expressão de ciclina D1 e expressão normal de c-myc, mesmo com expressão de p53 tipo mutante. Ainda, considerando o imunofenótipo semelhante nas glândulas com PIA, PIN e PC no que se refere aos reguladores da progressão do ciclo celular, reitera-se o potencial pré-maligno da PIA e PIN na próstata canina.(AU)

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (p<0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia.

PURPOSE: We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. MATERIALS AND METHODS: We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. RESULTS: Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (pv0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. CONCLUSIONS: This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Immunoexpression of cell cycle regulators in canine prostate with proliferative lesions / Imunoexpressão de reguladores do ciclo celular em próstatas caninas com alterações proliferativas

Immunostaining of p21, p27, p53, cyclin D1, c-myc was evaluated in normal canine prostate and prostate with proliferative disorders to verify the interaction between these regulators of cell cycle progression. From 106 samples of canine prostate obtained from a TMA block, 15 were considered normal, 16 diagnosed as benign prostatic hyperplasia (BPH), 30 as proliferative inflammatory atrophy (PIA), 20 as prostatic intraepithelial neoplasia (PIN), and 25 as prostatic carcinoma (PC). There was positive correlation between p21 and p27 for number of stained cells and staining intensity in all conditions and between c-myc and p53 in prostates with PIN. Considering the number of labeled cells, there was positive correlation between p21 and p53 in the normal prostate. Relative to the intensity of staining, there was positive correlation between p21 and p53 in prostate tissue with PIN and between p27 and c-myc in prostates with PIA. A negative correlation between c-myc and cyclin D1 was also identified in the glands with PIN, considering the number of labeled cells, and between p27 and c-myc in the prostates with PC for staining intensity. In conclusion, the expression of p21, p27, p53, cyclin D1 and c-myc varies according to type of proliferative lesion in canine prostate. Taken together, the results indicate low growth potential of the canine PC in the presence of p21 and p27 overexpression, cyclin D1 low expression and regular expression of c-myc, even with the expression of p53 mutant type. Further, it was possible reaffirm the premalignant potential of PIA and PIN in canine prostate.

A imunomarcação de p21, p27, p53, ciclina D1 e c-myc foi avaliada na próstata canina normal e com desordens proliferativas para verificar quanto a interação desses reguladores na progressão do ciclo celular. Um total de 106 amostras de próstata canina foi obtido a partir de um bloco de TMA, sendo 15 normais, 16 hiperplasia prostática benigna (HPB), 30 atrofia inflamatória proliferativa (PIA), 20 neoplasia intraepitelial prostática (PIN), e 25 carcinoma prostático (PC). Foi encontrada diferença na imunomarcação de p21, p27, ciclina D1 e p53 no epitélio acinar em relação aos diagnósticos. Houve correlação positiva entre p21 e p27 para as variáveis número de células marcadas e intensidade de imunomarcação em todos os diagnósticos (normal, HPB, PIA, PIN e PC), e entre c-myc e p53 nas próstatas com PIN. De acordo com o número de células marcadas, houve correlação positiva entre p21 e p53 na próstata normal. De acordo com a intensidade de imunomarcação houve correlação positiva entre p21 e p53 no tecido prostático com PIN e entre p27 e c-myc em próstatas com PIA. Foi observada correlação negativa entre c-myc e ciclina D1 nas glândulas com PIN, considerando o número de células marcadas, e entre p27 e c-myc na próstata com PC, para a variável intensidade de imunomarcação. Conclui-se que a expressão de p21, p27, p53, ciclina D1 e c-myc varia na próstata canina de acordo com o tipo de lesão proliferativa. Em conjunto, os resultados indicam baixo potencial de crescimento dos carcinomas da próstata canina quando há superexpressão de p21 e de p27, baixa expressão de ciclina D1 e expressão normal de c-myc, mesmo com expressão de p53 tipo mutante. Ainda, considerando o imunofenótipo semelhante nas glândulas com PIA, PIN e PC no que se refere aos reguladores da progressão do ciclo celular, reitera-se o potencial pré-maligno da PIA e PIN na próstata canina.

Relación entre ratio digital 2D: 4D y severidad preoperatoria del cáncer de próstata / Relationship between Digit Ratio (2D:4D) and Preoperative Severity of Prostate Cancer

El cociente entre la longitud del segundo y cuarto dedo (2D:4D) de la mano es un rasgo de dimorfismo sexual, presentando los hombres una ratio menor que las mujeres.1 Varios estudios de cohortes2,3 y un metaanálisis,4 han mostrado que la diferencia de género en la ratio de los dedos se asocia con la exposición de andrógenos prenatales. El cociente 2D:4D está inversamente relacionado a la exposición intrauterina de testosterona (T) y directamente relacionado a la de estradiol.2 Existe evidencia que afirma que la ratio 2D:4D podría ser un marcador válido para los niveles hormonales del adulto (T y estrógeno),3 aunque ese dato es controvertido.4Por esa razón, el cociente 2D:4D seha utilizado como un biomarcador no invasivo y retrospectivo para la exposición prenatal de andrógenos, y se ha correlacionado con una amplia gama de enfermedades como el autismo,5 así como la cognición visoespacial y la orientación sexual.6

The quotient between the length of the second and fourth finger (2D:4D) hand is a trait of sexual dimorphism, featuring the men a lower ratio than women.1 Several studies of the cohorts2,3 and a meta-analysis,4 have shown that the difference between The gender ratio of the fingers is associated with the exposure of prenatal androgens. The quotient 2D:4D is inversely related to intrauterine testosterone (T) exposure and directly related to that of estradiol.2 There is evidence which states that the 2D:4D ratio could be a valid marker for adult hormone levels (T and estrogen),3 although that data is controversial.4 For that reason, the 2D:4D quotient has been used as a noninvasive and retrospective biomarker for prenatal exposure to androgens, and it has been correlated with a wide range of diseases such as autism,5 as well as such as visuospatial cognition and sexual orientation.6

Minimal (Limited) Pseudohyperplastic Prostatic Adenocarcinoma in Needle Prostatic Biopsy.

BACKGROUND: Study of minimum adenocarcinoma has been done almost exclusively on conventional acinar adenocarcinoma. Pseudohyperplastic adenocarcinoma can be confused with benign lesions because of its well-differentiated appearance and has not been studied when the biopsy shows few malignant glands (limited carcinoma). METHODS: We reviewed 94 pseudohyperplastic adenocarcinomas diagnosed in prostatic biopsies for a period of 12 years and selected those measuring less than 1 mm or involving less than 5% of the biopsied tissue. We also reviewed 200 consecutive consultations. RESULTS: Four (4.2%) of the 94 cases were limited pseudohyperplastic adenocarcinomas, and 3 were from consultations. Three of them were mistaken for hyperplastic nodules, prostatic adenosis, or prostatic intraepithelial neoplasm. The number of glands varied between 6 and 50 (average 23). Three nodular histological patterns were identified-nodular, adenosis-like, and pseudohyperplastic carcinoma resembling prostatic intraepithelial neoplasia. The diagnosis of adenocarcinoma was not related to the number of neoplastic glands. Histological criteria that were useful included: crowded medium to large glands, papillary infoldings, branching glands, straight luminal borders, hyperchromatic nuclei, nucleomegaly, and apparent nucleoli. Areas of transition to conventional acinar adenocarcinoma were useful in recognizing four of these neoplasms, but were barely apparent in 2 of them. Hyperchromatic nuclei were found in all cases, whereas apparent nucleoli and nucleomegaly were only present in 4. CONCLUSIONS: The architectural and cytological criteria for limited acinar adenocarcinoma are only partially useful in interpreting minimum pseudohyperplastic adenocarcinomas. Knowledge of the criteria for malignancy in both neoplasms is important in order to avoid underdiagnosis of malignancy.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result

Abstract Introduction: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a positive second biopsy in males considered for re-biopsy. Material and Methods: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testosterone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. Results: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). Conclusion: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result.

INTRODUCTION: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a posi¬tive second biopsy in males considered for re-biopsy. MATERIAL AND METHODS: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testos¬terone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. RESULTS: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). CONCLUSION: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.