ESTANDARIZACIÓN DEL PROTOCOLO PARA LA DETECCIÓN DE LAS FUSIONES TMPRSS2: ERG Y DE LA EXPRESIÓN DE LOS GENES EZH2, SPINK-1 y NKX3.1 EN CÁNCER DE PRÓSTATA (CaP) / Protocol Standardization for Detection of TMPRSS2 Fusions: ERG and Gene Expression of EZH2, SPINK-1 and NKX3.1 in Prostate Cancer (PCa)

En la actualidad no existe una herramienta que permita diferenciar pacientes con cáncer de próstata (CaP) de mal pronóstico de aquellos con enfermedad indolente que sólo requieren un seguimiento controlado de la enfermedad. Debido a la coexistencia de diferentes focos premalignos y malignos en el CaP, el entendimiento sobre el proceso de carcinogénesis requiere de un mejor conocimiento. Actualmente, la heterogeneidad morfológica en CaP es evaluada con la puntuación de Gleason, la cual está fuertemente relacionada con el pronóstico de la enfermedad, sin embargo, esto es insuficiente por lo que se trabaja actualmente en identificación de alteraciones moleculares que permitan identificar subtipos que puedan establecer de manera más precisa el pronóstico del paciente. Este estudio preliminar buscó la estandarización del método de cuantificación en muestras prostáticas de FFPE de la expresión de los transcritos de posibles biomarcadores, como los oncogenes SPINK-1 y EZH2, el supresor tumoral NKX3.1, en conjunto con la determinación de la presencia/ausencia del gen de fusión TMPRSS2:ERG, ya que estos transcritos se encuentran involucrados en aparentes eventos excluyentes de la evolución natural del CaP, que apoyan la posibilidad de una clasificación molecular para esta enfermedad.

At present doesn't exist tool to differentiate patients with prostate cancer (PCa) of poor prognosis of those with indolent disease that only require a controlled monitoring of the disease. Because of the coexistence of different premalignant and malignant foci in CaP, the understanding of the carcinogenesis process requires a better understanding. Currently, the morphological heterogeneity in PCa is evaluated with Gleason score, which is closely related to the prognosis of the disease, but this is insufficient so it is currently to work on identifying molecular alterations to identify subtypes that can establish more precisely the patient's prognosis. This preliminary study aimed to standardization of the method of quantification in prostatic samples of FFPE of expression of transcripts of possible biomarkers, such as the oncogenes, SPINK-1 y EZH2, the tumour suppressor, NKX3.1, together with the determination of the presence/absence of gene fusion, TMPRSS2:ERG, being that these transcripts are involved in apparent exclusive events of the natural evolution of PCa, that support the possibility of a molecular classification for this disease.

Matrix metalloproteinases 2 and 9 expression in canine normal prostate and with proliferative disorders / Expressão de metaloproteinases de matriz 2 e 9 na próstata canina normal e com lesões proliferativas

In this study the expression of metalloproteinases 2 (MMP-2) and 9 (MMP-9) in canine normal prostates and with proliferative disorders was evaluated to verify the role of these enzymes in extracellular matrix remodeling (ECM) and in the tissue invasion process. A total of 355 prostatic samples were obtained, from which 36 (10.1%) were normal prostates, 46 (13.0%) with benign prostatic hyperplasia (BPH), 128 (36.1%) with proliferative inflammatory atrophy (PIA), 74 (20.8%) with prostatic intraepithelial neoplasia (PIN), and 71 (20.0%) with prostatic carcinoma (PC). Difference in cytoplasmic immunohistochemical staining of MMP-2 and MMP-9 between acinar epithelium and periacinar stroma was found regarding the different diagnosis. The correlation between MMP-2 and MMP-9 expression in relation to the number of labeled cells in acinar epithelium and periacinar stroma, as well as to the staining intensity in the periacinar stromal cells was evidenced in canine prostates with PIA. In conclusion, MMP-2 and MMP-9 expression has a variation in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in those with PIA, PIN and PC. Moreover, the inflammatory microenvironment of the PIA has influence in the activity of both enzymes.

Este estudo teve como objetivo avaliar a expressão das metaloproteinases 2 (MMP-2) e 9 (MMP-9) em próstatas caninas normais e com desordens proliferativas, verificando o papel dessas enzimas na remodelação da matriz extracelular (MEC) e no processo de invasão tecidual. Um total de 355 amostras prostáticas foram obtidas, sendo 36 (10,1%) normais, 46 (13,0%) com hiperplasia prostática benigna (HPB), 128 (36,1%) com atrofia inflamatória proliferativa (PIA), 74 (20,8%) com neoplasia intraepitelial prostática (PIN) e 71 (20,0%) com carcinoma prostático (CP). Houve diferença de imunomarcação citoplasmática para MMP-2 e MMP-9 entre o epitélio acinar e o estroma periacinar, quanto aos diferentes diagnósticos. Observou-se correlação entre a expressão de MMP-2 e MMP-9 em relação ao número de células marcadas no epitélio acinar e estroma periacinar, bem como para a intensidade de marcação das células estromais periacinares em próstatas caninas com PIA. Conclui-se que há variação na expressão de MMP-2 e MMP-9 em próstatas caninas de acordo com a lesão, com menor expressão em próstatas caninas normais e com HPB, e maior naquelas com PIA, PIN e CP. Ainda, o microambiente inflamatório na PIA influencia a atividade de ambas as enzimas.

Características histopatológicas de la neoplasia intraepitelial prostática / Histopathologic characteristics of the prostatic intraepithelial neoplasia

La enfermedad de la próstata es hoy un problema de salud por su elevada morbilidad y mortalidad en adultos mayores de 50 años. Acerca de ello se realizó este estudio descriptivo y transversal sobre los hallazgos histopatológicos de neoplasia intraepitelial prostática en las biopsias de próstata útiles, recibidas para su análisis en el Departamento de Anatomía Patológica del Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo de Santiago de Cuba durante el bienio 2008-2009. Entre los principales resultados sobresalió la confirmación, por la mencionada vía, de hiperplasia fibroadenomatosa de la próstata, lesiones prostáticas, carcinomas y otras alteraciones en esa glándula masculina. Los datos obtenidos ratificaron que el diagnóstico a través de muestras de tejido de neoplasia intraepitelial prostática, constituye una de las formas en que los patólogos pueden contribuir a la oportuna detección del carcinoma prostático.

The prostate disease is a health problem nowadays due to its high morbidity and mortality in adults older than 50 years. Based on this, a descriptive and cross sectional study was carried out on the histopathologic findings of the prostatic intraepithelial neoplasia in the useful prostate biopsies examined in the Pathology Department of Dr Ambrosio Grillo Portuondo Clinical Surgical Teaching Hospital in Santiago de Cuba during the biennium 2008-2009. Among the main results there were: the confirmation of prostate fibroadenomatous hyperplasia, prostatic lesions, carcinomas and other alterations in that male gland, all through biopsy. The obtained data confirmed that the diagnosis through samples from the prostatic intraepithelial neoplasia tissue, constitutes one of the ways by which pathologists can contribute to the opportune detection of the prostatic carcinoma.

Adenocarcinoma incidental de próstata en resección transuretral por causa benigna: Hospital de San José, julio 2006 a marzo 2008 / Incidental prostatic adenocarcinoma during transurethral resection for a bening cause: San Jose Hospital, july 2006 - march 2008

La resección transuretral de próstata es un procedimiento común para tratar patologías urinarias obstructivas benignas. Al material obtenido se le practica estudio histológico para confirmar la naturaleza benigna, pero en algunos casos se ha encontrado como hallazgo incidental un adenocarcinoma en estadios tempranos. No se sabe con claridad cuánto material debe procesarse o si la cantidad de tejido examinado aumenta la posibilidad de encontrar cáncer. El objetivo de este trabajo es determinar la frecuencia de adenocarcinoma incidental de próstata en pacientes sometidos a RTU por causa benigna. Reune 196 casos de RTU en los que se procesó en una segunda fase todo el tejido restante obtenido, describiendo las variables edad, peso del espécimen, número de láminas procesadas, niveles de PSA y categoría diagnóstica, la cual fue clasificada como negativa para maglinidad, PIN alto de grado y adenocarcinoma de próstata estadios T1a y T1b. Se encontró que la frecuencia de cáncer próstata en pacientes a quienes se les realizó RTU por hiperplasia prostática benigna en el Hospital de San José fue muy baja, dos pacientes de 71 y 80 años, además de otro que corresponde a una neoplasia intraepitelial de alto grado (PIN de AG) con niveles normales de PSA, lo que evidencia que la frecuencia es menor que la reportada en la literatura internacional.

Transurethral resection of the prostate (TURP) is a common procedure performed to treat benign urinary obstruction conditions. The specimen obtained undergoes hystologic work-up to confirm benign nature, but in some cases, an early-stage adenocarcinoma is found incidentally. It is not clearly known how much material must be processed or if the amount of tissue examined increases likelihood of finding cancer. The purpose of this work is to determine the frequency rate of incidental prostatic adenocarcinoma in patients who undergo TURP for a benign cause. It gathers 196 cases of TURP in which all the remaining tissue obtained underwent a second phase work-out, considering variables as age, weight of specimen, number of slides processed, PSA levels and diagnostic category, which was classified as negative for malignancy, high-grade prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma in stages T1a and T1b. It was evidenced that the frequency of prostate cancer in patients who underwent TURP for benign prostatic hyperplasia at the San José Hospital was very low, consisting of two patients 71 and 80 years old, as well as one that corresponds to a high-grade prostatic intraepithelial neoplasia (PIN of AG) with normal PSA levels, which evidences that our frequency rate is smaller than that reported in international literature.