Humoral and Cellular Immunology in Human Prostate Cancer: Plasma Cells and T and B Lymphocytes / Inmunología Humoral y Celular en el Cáncer de Próstata Humano: Células Plasmáticas y Linfocitos T y B

SUMMARY: In solid and malignant tumors, innate and adaptive immunity are combined in antitumor responses. This study aimed to analyze the activation of plasma cells and the correlation between the infiltration of B and T lymphocytes with the degree of malignancy or Gleason grade in human prostate biopsies diagnosed with cancer. Prostate cancer biopsies were obtained from the Clinical Hospital of Universidad de Chile (n=70), according to the bioethical norms of the institution. Histological sections of 5µm thickness were processed for immunohistochemistry with primary antibodies against BL and total TL (HRP/DAB). Recognition and quantification were performed under a Leica DM750 optical microscope. Microsoft Excel and GraphPad software were used for the statistical study. Correlation coefficient (Pearson) and mean comparison tests (Kruskal-Wallis and Dunn) and p≤ 0.05 were developed. B and T lymphocyte populations were inversely interregulated in prostate cancer (Gleason) (r= -0.46). Their relationship with Gleason grade is variable according to lymphocyte type (LB vs. Gleason r= -0.0.47 and LT vs. Gleason r= -0.21). Histological diagnosis of prostate cancer correlates with a predominance of LT. The malignancy of the pathology correlates with a predominance of LTs, according to the Gleason grade. The increased knowledge of B and T lymphocyte infiltration and plasma cell activation could be used to better target clinical trials on treatments based on immune system responses. Immunotherapy could be a new paradigm to apply better antitumor therapy strategies.

En tumores sólidos y malignos, la inmunidad innata y adaptativa se combinan en respuestas antitumorales. Este estudio tuvo como objetivo analizar la activación de células plasmáticas y la correlación entre la infiltración de linfocitos B y T con el grado de malignidad o grado de Gleason en biopsias de próstata humana diagnosticadas con cáncer. Las biopsias de cáncer de próstata se obtuvieron del Hospital Clínico de la Universidad de Chile (n=70), de acuerdo con las normas bioéticas de la institución. Secciones histológicas de 5 µm de espesor fueron procesadas para inmunohistoquímica con anticuerpos primarios contra LB y LT total (HRP/DAB). El reconocimiento y las cuantificaciones se realizaron bajo un microscopio óptico Leica DM750. Para el estudio estadístico se utilizaron los programas Microsoft Excel y GraphPad. Se desarrollaron pruebas de coeficiente de correlación (Pearson) y comparación de medias (Kruskal-Wallis y Dunn) y p≤ 0.05. Los resultados muestran que las poblaciones de linfocitos B y T están inversamente interreguladas en el cáncer de próstata (r= -0,4578). Su relación con el grado de Gleason es variable según el tipo de linfocito (LB vs Gleason r= -0,47* y LT vs Gleason r= -0,21). Se concluye que la malignidad del cáncer de próstata se correlaciona con un predominio de LT, versus el grado de Gleason. El mayor conocimiento de la infiltración de linfocitos B y T y la activación de células plasmáticas podría aprovecharse para una mejor orientación de ensayos clínicos en tratamientos basados en las respuestas del sistema inmunitario. La inmunoterapia podría ser un nuevo paradigma para aplicar mejores estrategias de terapias antitumorales.

Improving adenoviral vectors and strategies for prostate cancer gene therapy

Gene therapy has been evaluated for the treatment of prostate cancer and includes the application of adenoviral vectors encoding a suicide gene or oncolytic adenoviruses that may be armed with a functional transgene. In parallel, versions of adenoviral vector expressing the p53 gene (Ad-p53) have been tested as treatments for head and neck squamous cell carcinoma and non-small cell lung cancer. Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach. To achieve better functionality, improvements in the gene transfer system and the therapeutic regimen may be required. We have developed adenoviral vectors whose transgene expression is controlled by a p53-responsive promoter, which creates a positive feedback mechanism when used to drive the expression of p53. Together with improvements that permit efficient transduction, this new approach was more effective than the use of traditional versions of Ad-p53 in killing prostate cancer cell lines and inhibiting tumor progression. Even so, gene therapy is not expected to replace traditional chemotherapy but should complement the standard of care. In fact, chemotherapy has been shown to assist in viral transduction and transgene expression. The cooperation between gene therapy and chemotherapy is expected to effectively kill tumor cells while permitting the use of reduced chemotherapy drug concentrations and, thus, lowering side effects. Therefore, the combination of gene therapy and chemotherapy may prove essential for the success of both approaches.

Avaliação de margens circunferenciais, extensão extraprostática e escore de Gleason em produtos de prostatectomia radical examinados por método de inclusão parcial e método de inclusão parcial com inclusão suplementar de toda periferia da próstata / Evaluation of circumferential margins, extraprostatic extension and Gleason score in radical prostatectomy products examined by partial inclusion method and partial inclusion method with supplementary inclusion of all periphery of the prostate

INTRODUÇÃO: Estudos recentes sugerem que a inclusão parcial deixa de detectar até 21% e 47% de margens circunferenciais positivas (MCP) e extensão extraprostática (EEP),respectivamente. Kim et al (2009) sugerem que a inclusão de toda a periferia da próstata (3mm de espessura) previne a falha na detecção de MCP e EEP. OBJETIVO: Comparar um método de inclusão parcial de produtos de prostatectomia radical com a inclusão suplementar de toda periferia da próstata. METODOLOGIA: Foram revistos 148 casos de produtos de prostatectomia radical em dois serviços de patologia de Salvador-BA, após a adoção de um protocolo incluindo 3mm de tecido periférico da próstata. Foi avaliado se após a análise das lâminas histológicas adicionais houve mudança na margem, extensão extraprostática,escore de Gleason e extensão da MCP e EEP. RESULTADOS: O método de inclusão parcial deixou de detectar 29% do envolvimento de MCP e 20% dos casos com EEP. Mudança de acometimento focal para extenso foi observada em 11/21 (52%) casos de MCP e em 5/13 (38%) dos casos de EEP. Mudança no escore de Gleason foi incomum (5%). CONCLUSÃO:Os resultados mostram a importância da inclusão de toda a periferia da próstata para análise microscópica quando métodos de inclusão parcial são adotados.

BACKGROUND: Recent data suggest that up to 21% of positive circumferential margins (PCM) and 47% of extraprostatic extension (EPE) samples may be missed when partial embedding methods are employed. Kim and colleagues (2009) suggested that total inclusion of the periphery (3 mm rim) of the prostate prevented the failure to detect PCM and EPE. DESIGN: Radical prostatectomy specimen (n = 148) slides were reviewed after adoption of a protocol that included a 3 mm rim of peripheral tissues. We evaluated whether the analysis of supplemental slides of prostate periphery changed margin status, presence of EPE, Gleason score and extent of PCM and EPE. RESULTS: Partial sampling resulted in missing 29% of PCM and 20% of EPE without using data from the supplemental slides of prostate periphery. Changes from focal to extensive disease were found in 11/21 (52%) cases of positive circumferential margins and in 5/13 (38%) cases of extraprostatic extension. Changes in the Gleason score were uncommon (5%). CONCLUSIONS: These results indicate the importance of including all the prostate peripheral tissue for microscopic analysis when partial embedding methods are adopted.

Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.

Ancestralidade genética e genes de susceptibilidade em portadores de câncer de próstata do Estado da Bahia / Genetic ancestry and susceptibility genes in patients with prostate cancer of Bahia

O Cancêr de Próstata (CaP) é um dos tipos de neoplasias mais frequentes nos homens em todo o mundo e também na população masculina brasileira. A incidência, mortalidade e agressividade do CaP são maiores em homens negros. De acordo com o IBGE a Bahia é o estado que apresenta a maior porcentagem de população afrodescendente e os indivíduos que moram em Salvador apresentam maior ancestralidade africana que os nascidos no interior do estado. O presente estudo verificou a associação entre maior ancestralidade genética africana e genes de suscetibilidade ao CaP em pacientes do estado da Bahia oriundos do setor particular e público de serviço à saúde. Participaram do estudo 189 homens com CaP, sendo 82 atendidos no serviço privado e 107 no serviço público e 112 homens saudáveis atendidos no serviço público. Foram utilizados 9 marcadores informativos de ancestralidade (AIM) para estimar a ancestralidade genética e quatro genes de suscetibilidade: CYP3A4, CYP17, GSTM1 e GSTT1...

Prostate cancer (PCa) is one of the most common types of cancer in men worldwide and also in Brazilian male population. The incidence, mortality and PCa aggressiveness are higher in black men. According to the IBGE, Bahia is the state with the highest percentage of people of African descent and people who live in Salvador has the largest African ancestry born in the state. The present study sought to determine the association between African ancestry and greater susceptibility genes in PCa patients of Bahia state from public and private sector health service. The study included 189 men with PCa, 82 served in the private and 107 public service and 112 healthy men served in the public service. We used ancestry informative markers 9 (AIM) to estimate genetic ancestry and 4 susceptibility genes, among them: CYP3A4, CYP17, GSTM1 e GSTT1...

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer

Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

Enhanced inhibition of murine prostatic carcinoma growth by immunization with or administration of viable human umbilical vein endothelial cells and CRM197

Vaccination with xenogeneic and syngeneic endothelial cells is effective for inhibiting tumor growth. Nontoxic diphtheria toxin (CRM197), as an immunogen or as a specific inhibitor of heparin-binding EGF-like growth factor, has shown promising antitumor activity. Therefore, immunization with or administration of viable human umbilical vein endothelial cells (HUVECs) combined with CRM197 could have an enhanced antitumor effect. Six-week-old C57BL/6J male mice were vaccinated with viable HUVECs, 1 x 10(6) viable HUVECs combined with 100 μg CRM197, or 100 μg CRM197 alone by ip injections once a week for 4 consecutive weeks. RM-1 cells (5 x 10(5)) were inoculated by sc injection as a preventive procedure. During the therapeutic procedure, 6-week-old male C57BL/6J mice were challenged with 1 x 10(5) RM-1 cells, then injected sc with 1 x 10(6) viable HUVECs, 1 x 10(6) viable HUVECs + 100 μg CRM197, and 100 μg CRM197 alone twice a week for 4 consecutive weeks. Tumor volume and life span were monitored. We also investigated the effects of immunization with HUVECs on the aortic arch wall and on wound healing. Vaccination with or administration of viable HUVECs+CRM197 enhanced the inhibition of RM-1 prostatic carcinoma by 24 and 29 percent, respectively, and prolonged the life span for 3 and 4 days, respectively, compared with those of only vaccination or administration with viable HUVECs of tumor-bearing C57BL/6J mice. Furthermore, HUVEC immunization caused some damage to the aortic arch wall but did not have remarkable effects on the rate of wound healing; the wounds healed in approximately 13 days. Treatment with CRM197 in combination with viable HUVECs resulted in a marked enhancement of the antitumor effect in the preventive or therapeutic treatment for prostatic carcinoma in vivo, suggesting a novel combination for anti-cancer therapy.

Caracterização funcional da interação entre as proteínas CTSP-1 e CTCF / Functional characterization of the interaction between the proteins CTSP-1 and CTCF

Os antígenos cancer-testis (CT) são proteínas imunogênicas expressas em tecido gametogênico e em diferentes tipos de tumor, sendo considerados candidatos promissores para a imunoterapia do câncer. Entretanto, pouco se sabe sobre a função desses antígenos na tumorigênese. Em 2006, identificamos CTSP-1 como um novo antígeno CT, frequentemente expresso em vários tumores. Nesse trabalho, investigamos a função de CTSP-1 por meio da identificação de proteínas expressas em tumores de próstata e que são capazes de interagir fisicamente com esse antígeno. Demonstramos que CTSP-1 interage com a proteína CTCF em ensaios de duplo-híbrido em leveduras, pulldown e de co-localização e, em seguida, analisamos o impacto da superexpressão de CTSP-1 no controle da expressão de genes CT mediada por CTCF e na progressão do ciclo celular. Utilizando o CT NY-ESO-1 como modelo, demonstramos que a superexpressão de CTSP-1 não altera os níveis endógenos de NY-ESO-1 na linhagem celular tumoral H1299. Por outro lado, observamos que a superexpressão de CTSP-1 48h após as transfecções em H1299 induz um bloqueio do ciclo em G0/G1, reduzindo a capacidade clonogênica dessas células por um mecanismo dependente dos níveis de expressão de CTSP-1. Resultados semelhantes não foram observados em ensaios com clones superexpressando CTSP-1 estavelmente, o que sugere que eles tenham se originado de células que conseguiram escapar do bloqueio em G0/G1. Resultados preliminares sugerem que a redução da capacidade clonogênica das células H1299 que superexpressam CTSP-1 48h após as tansfecções não está associada à ocorrência de morte por apoptose.

Cancer-testis (CT) antigens are immunogenic proteins expressed in gametogenic tissues and in different histological types of tumors, being considered promising candidates for cancer immunotherapy. However, little is known about their role in tumorigenesis. In 2006, we identified CTSP-1 as a novel CT antigen, frequently expressed in different types of tumors. In this work, we investigated the functional role of CTSP-1 through the identification of proteins expressed in prostate tumors and that physically interact with this tumor antigen. We demonstrate that CTSP-1 interacts with the CTCF protein using the yeast two-hybrid system, pulldown and co-localization assays and have further analyzed the impact of CTSP-1 overexpression on the expression of CT genes mediated by CTCF and on the cell cycle progression. Using the CT antigen NY-ESO-1 as a model, we showed that the CTSP-1 overexpression does not alter the endogenous levels of NY-ESO-1 in the tumor cell line H1299. On the other hand, we observed that the overexpression of CTSP-1 in H1299 cells 48h after the transfections induces a cell cycle arrest in G0/G1 and reduces the clonogenic capacity of these cells by a mechanism dependent on the CTSP-1 expression levels. Similar results were not observed for cell clones stably overexpressing CTSP-1, suggesting that these clones have arisen from cells that managed to escape cell cycle arrest in G0/G1. Preliminary results suggest that the reduced clonogenic capacity of H1299 cells expressing CTSP-1 and analyzed 48h after the transfections is not associated with cell death by apoptosis.

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil(R)), Prostaglandin E2, and Interferon-alpha as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil(R)) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

Refining the assessment of the sensitivity and specificity of diagnostic tests, with applications to prostate cancer screening and non-small cell lung cancer staging

Los cálculos del rendimiento de las pruebas diagnósticas suelen presentarse en tablas de 2x2 con filas horizontales para los resultados positivos y negativos obtenidos con la prueba evaluada, y con columnas verticales para los resultados positivos y negativos obtenidos con el patrón de oro. Esta manera de presentar los datos visualmente, así como las sensibilidades y especificidades basadas en ella, le imprimen carácter binario a la prueba y al patrón de oro. Pero cuando los resultados de la prueba pertenecen a una de varias categorías ordenadas, a menudo se utilizan curvas de las características funcionales de la prueba (o curvas ROC, por receiver operator characteristic curve) para indicar que esta no es binaria. Tratar el patrón de oro como si fuese binario también es problemático porque implica que toda enfermedad se comporta uniformemente, con el resultado de que a todos los casos se les trata como si fuesen intercambiables. No obstante, hay ciertos tumores, por ejemplo, que exigen más tratamiento que otros y que por lo tanto también exigen mayor detección. En el presente trabajo proponemos el uso de una tabla refinada que clasifica a los tumores en función de lo que se sabe de su susceptibilidad al tratamiento, con lo cual se pretende lograr una evaluación más informativa de las pruebas que la proporcionada por la tabla de 2x2. A manera de ejemplo presentamos una tabla de 2x3 en la cual se refina la medición del antígeno específico de la próstata (AEP) teniendo en cuenta el resultado de la palpación rectal. Dicho resultado se usa como indicador de la necesidad de tratar los cánceres prostáticos que se detectan o que no se detectan mediante la prueba del AEP. Un segundo ejemplo aplica los mismos conceptos a la tomografía por emisión de positrones y a la tomografía computadorizada cuando se usan para la estadificación del cáncer pulmonar no microcítico. Se usaría más información si se adoptara la estructura de 2x3 para configurar la tabla.

Role of the phosphatase PP4 in the activation of JNK-1 in prostate carcinoma cell lines PC-3 and LNCaP resulting in increased AP-1 and EGR-1 activity

The specific signaling connections between the mitogen-activated protein kinases (MAPK) such as c-Jun N-terminal kinase (JNK-1) and phosphatases PP4 and M3/6, affecting the family of early nuclear factors, is complex and remains poorly understood. JNK-1 regulates cellular differentiation, apoptosis and stress responsiveness by up-regulating early nuclear factors such as c-Jun, a member of the activating protein (AP-1) family, and the Early Growth Factor (EGR-1). C-Jun, when phosphorylated by c-Jun N-terminal kinase (JNK-1) associates with c-Fos to form the AP-1 transcription factor that activates gene expression. We have investigated the regulation of the JNK-1 kinase by co-transfecting phosphatases PP4 and M3/6 in prostate cancer cell lines PC-3 and LNCaP, which have been previously stimulated with human EGF or cisplatin. Co-transfections of plasmids expressing the JNK-1 and the serine/threonine phosphatases PP4 resulted in a significant increase in JNK-1 activity in both PC3 and LNCaP cells. In contrast, co-transfection of JNK-1 with the dual specific phosphatase serine/threonine M3/6 showed only a marginal effect in JNK-1 activity. The phosphatase M3/6 also failed in blocking the induction of JNK-1 activity observed in presence of PP4. The higher activity of JNK-1 was associated with increased activities of the factors c-Jun/AP-1 and EGR-1. This suggests that JNK-1 activity in PC-3 and LNCaP cells requires not only active PP4 for stable maintenance but also suggests that the relative degree of phosphorylation of multiple cellular components is the determinant of JNK-1 stability.

Immunohistochemical expression of survivin and Bcl-2 in prostatic adenocarcinoma

The present work was carried out to detect the expression of survivin and Bcl-2 in twenty cases of prostatic adenocarcinoma, and to determine its correlation with the different clinicopathologic parameters including age of the patient, serum prostate -specific antigen [PSA] level, clinical stage and Gleason score. Positive staining for both survivin and Bcl-2 was seen as brown cytoplasmic staining. A semiquantitative method based on both intensity and distribution of staining was used to score immunohistochemical positivity. 75% and 35% of the studied cases of prostatic adenocarcinoma showed positive staining for survivin and Bcl-2 respectively. 20% of cases showed concomitant expression of both survivin and Bcl-2. Expression of survivin alone was detected in 55% of cases, while 15% of cases expressed Bcl-2 only. No correlation was found between survivin and Bcl-2 expression [p=0.176]. A significant association was detected between survivin expression and the Gleason score of prostatic adenocarcinoma, where p=0.004. Another significant correlation was found between Bcl-2 expression and the tumor stage [p=0.007]. Overexpression of survivin and Bcl-2 in prostatic adenocarcinoma indicate their possible role in tumorigenicity and/or tumor progression. A definite correlation was found between survivin expression and the Gleason score of prostatic adenocarcinoma. In addition,a significant correlation was detected between Bcl-2 expression and tumor stage. Survivin and Bcl-2 may serve as targets for apoptosis-based therapy of prostatic adenocarcinoma

Prostate specific antigen as tumor marker: relationship with histologic grading.

PSA is emerging as the best marker in oncology and had a profound impact on all aspects of prostate cancer care. From clinically suspected prostate tumor, 395 serum samples were taken out and estimated for serum PSA. Among elevated serum PSA, 98 were correlated with histologic findings. 42(42.8%) cases were BHP among 98 cases and 78.7% had serum PSA level within 10 ng/ml. 5 patients (5.1%) had PIN histologically, 3(60%) of which had PSA level upto 10 ng/ml and 2(40%) had serum PSA upto 20 ng/ml. 51(52%) were adenocarcinoma prostate of different grades and PSA level varies from less than 10 ng/ml to more than 50 ng/ml which almost correlates with the tumor grades.

Autoanticuerpos contra antígeno específico en hiperplasia benigna y cáncer de próstata / Autoantibodies againts prostatic specific antigen in benign hyperplasia and prostate cancer

Por medio de ELISA (Enzyme linked immunosorbent assay), se llevó a cabo la determinación de autoanticuerpos contra el antígeno específico de próstata en los sueros de dos grupos de pacientes: uno con hiperplasia prostática benigna y otro con cáncer de próstata. Los resultados encontrados confirman la presencia de autoanticuerpos en los sueros de ambos grupos, sin embargo, no se demostró diferencia estadísticamente significativa en la concentración de autoanticuerpos contra el antígeno específico de próstata

Utilidad de la fracción libre del antígeno prostático específico en la detección del cáncer de la próstata / Usefulness of free prostatic specific antigen in the detection of prostate cancer

Background: The predictive value of prostate specific antigen for prostate cancer, when levels are between 4 and 10 ng/ml, is low. Within these range of values, some authors recommend the measurement of the free fraction of the antigen to improve its predictive capacity. Aim: To evaluate the predictive value of the free fraction in subjects with prostate specific antigen values between 4 and 10 ng/ml. Patients and methods: One hundred and forty subjects with prostate specific antigen between 4 and 10 ng/ml were evaluated. All were subjected to transrectal ultrasound examination with biopsies and the free fraction of the antigen was measured by enzyme immuno assay. Results: Cancer was diagnosed in 36 subjects, all others had a benign prostatic hyperplasia. Mean prostate specific antigen values were 7.4 and 7.1 ng/ml in patients with cancerand hyperplasia, respectively. The percentage of free prostatic specific antigen was 9.8 and 19.8 percent in subjects with cancer and hyperplasia respectively (p <0.001). Using receiver operating characteristic (ROC) curves, a free prostate specific antigen of 13 percent was the best cutoff value for predicting prostate cancer. Conclusions: In subjects with prostate specific values between 4 and 10 ng/ml, the measurement of the free fraction of this antigen can improve the predictive value of this parameter for the detection of prostate cancer

Cuantificación de receptores androgénicos como factor pronóstico en pacientes con cáncer de próstata / Quantitative determination of tissue androgenic receptors as a prognostic factor in patients who have prostatic carcinoma

El cáncer de próstata es el tumor maligno más común en la población masculina mayor de 50 años y está considerado como la segunda causa de muerte por cáncer. El 70 por ciento de los pacientes al momento de su diagnóstico presentan enfermedad avanzada por lo que la gran mayoría de ellos recibirán tratamiento hormonal, predecir qué pacientes responderán a éste es el objetivo de este estudio. De enero de 1991 a junio de 1994 se atendieron 40 pacientes con diagnóstico de cáncer de próstata estadio D2, con un seguimiento mínima de dos años. Se reconfirmó la gradación de Gleason y de sus bloques de parafina se realizó la cuantificación de los receptores por técnica de inmunoeroxidas. Presentaron buena respuesta 25 casos (62.5 por ciento) es decir más de dos años de sobrevida libre de actividad tumoral y mala respuesta 15 (37.5 por ciento) quienes presentaron actividad tumoral antes de los dos años o que presentaron nula respuesta al tratamiento. La edad de nuestra población fue de 71 (ñ 19) años, el antígeno prostático específica presentó un rango variable entre 11.2 y 900 ng/ml con una mediana de 41.6 ng/ml. En la gran mayoría de nuestros pacientes su gradación de Gleason fue de 2, 3 y 4. La cuantificación de receptores en los casos con buena respuesta de 121.5 /ñ 21.3). La calidad de la respuesta al tratamiento fue directamente proporcional al número de receptores (p<0.005), de donde concluimos que la determinación de dichos receptores sirve como factor pronóstico en pacientes con cáncer de próstata y que aún más puede predecir cuáles pacientes serán buenos candidatos al tratamiento hormonal

Expresión de la proteína del gen supresor de tumores p53 en el carcinoma de próstata / Expression of the supressor gene protein of p53 tumors in prostatic carcinoma

El cáncer de la próstata es una de las neoplasias más frecuentes en hombres mayores de 50 años. La mutación y expresión del gen supresor de tumores p53 ha sido demostrado en la carcinogénesis de múltiples neoplasias y en alrededor del 40 por ciento de los cánceres de la próstata. El objeto de este trabajo es determinar la frecuencia de la expresión del gen p53 en el carcinoma prostático. Se estudia la expresión de la proteína p53 en 35 carcinomas prostáticos mediante la técnica de inmunohistoquímica con anticuerpo monoclonal. Los pacientes se distribuyeron por etapas clínicas: Etapa A = 4 casos; Etapa B = 5 casos; Gleason entre 4 y 7 y el 16 por ciento entre 8 y 10. El promedio de edad fue 70,7 años (límites 53-85 años). No se observó tinción positiva en ninguno de los controles ni en los tumores en etapas A y B. Se observó tinción positiva de la proteína del gen p53 en 11 de los 35 casos (31,4 por ciento), 17 por ciento en los en Etapa C y un 64,2 por ciento tumores en los en Etapa D (p = 0,01). No se observó diferencia respecto del índice de Gleason aun cuando los tumores mejor diferenciados presentaron menor positividad. Nuestros resultados muestran que la proteína del gen supresor de tumores p53 no guarda relación con el índice de Gleason y sólo se observa en tumores avanzados, especialmente en la Etapa D, y su determinación puede contribuir significativamente a una mejor evaluación preoperatoria de los pacientes

Antígeno prostático y cáncer: una visión actualizada / Prostatic antigen and cancer: an updated view

El cáncer prostático constituye un importante problema de salud pública, cuya magnitud ha ido aumentando gradualmente de acuerdo a la prolongación de las espectativas de vida. El antígeno prostático específico es el recurso diagnóstico de mayor utilidad actualmente disponible. Es también de utilidad en la etapificación y monitorización de la evolución del cáncer prostático. El presente trabajo informa acerca de qué es el antígeno prostático y cómo debe ser utilizado en la detección precoz del cáncer de la próstata órgano-localizado, así como en el manejo y control de los pacientes sometidos a prostatectomía radical y a terapia de privación androgénica

Valor del Gleason preoperatorio y del antígeno prostático específico como factores predictivos de metástasis ganglionares en el cáncer de próstata / Value of preoperatory Gleason and of the prostatic specific antigen with predictive factors of lymph node metastases in prostate cancer

Se ha demostrado el significado pronóstico que tiene el volumen tumoral, la invasión de vesículas seminales, compromiso del tejido periprostático y el compromiso de los ganglios linfáticos regionales en el pronóstico del cáncer de próstata, sin embargo el único método realmente confiable para conocer el estado de los mismos continua siendo el análisis anátomo patológico. El objetivo de este trabajo es buscar si existe alguna correlación entre el grado de diseminación tumoral (compromiso ganglionar) y algunas variables de las que se dispone en el preoperatorio como el valor del APE y el Gleason de la biopsia preoperaoria. Para ello se analizó en forma retrospectiva los resultados de 147 pacientes que fueron sometidos a Prostatectomía radical en un período de 9 años. El análisis de los resultados mostró que no existe un valor predictivo en el valor del Gleason preoperatorio conla presencia de ganglios linfáticos comprometidos (p = 0.06), el valor del APE promedio preoperatorio si presentó una correlación positiva con la presencia de metástasis ganglionares (p = 0.006), aunque existe una gran desviación standart en los valores registrados. Utilizando estos valores pudimos construir un modelo de regresión logística, por medio de la cual calcular la probabilidad de tener compromiso linfático conociendo el valor del APE preoperatorio con un valor concordante del 75 por ciento