Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance.

INTRODUCTION AND OBJECTIVE: Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. MATERIALS AND METHODS: Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. RESULTS: Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV)≤60cc and the number of positive cylinders >1 in diagnostic biopsy (P=.05) were associated with higher reclassification rate in univariate analysis (P<.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, P=.04; >1 positive cylinder at diagnostic biopsy: OR 2.48, P=.03). CONCLUSIONS: It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series.

Factores clínicos e histológicos predictores de reclasificación en pacientes incluidos en programa de vigilancia activa de cáncer de próstata / Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance

Introducción y objetivo La vigilancia activa (VA) se ha establecido como estrategia terapéutica en pacientes con cáncer de próstata de bajo riesgo. Se han identificado factores demográficos y anatomopatológicos que aumentan la probabilidad de reclasificar a los enfermos. Materiales y métodos Se han recogido datos analíticos e histopatológicos de 116 pacientes incluidos en VA desde 2014. Se ha realizado un análisis univariante con X2, t de Student y Tau de Kendall, un análisis multivariante según regresión logística y se han calculado las curvas de Kaplan-Meier. Resultados De los 116 pacientes en VA, la mediana de edad al diagnóstico fue 66 años y la mediana de seguimiento fueron 13 meses (2-72). De todos ellos, 61 (52,6%) siguen en vigilancia mientras que 55 (47,4%) han salido del programa, la mayoría por progresión histológica (52 pacientes [45,2%]), realizándose prostatectomía radical en 27 (49,1%). El volumen prostático (Vp) ≤ 60cc y el número de cilindros positivos >1 en la biopsia diagnóstica (p = 0,05) se asociaron con mayor tasa de reclasificación en el análisis univariante (p < 0,05). En el análisis multivariante, estas dos variables se correlacionaron significativamente con una mayor tasa de reclasificación (Vp ≤ 60 cc: OR 4,39, p = 0,04; >1 cilindro positivo en la biopsia diagnóstica: OR 2,48, p = 0,03). Conclusiones Se ha objetivado que el volumen ecográfico inicial y el número de cilindros positivos en la biopsia diagnóstica son factores de riesgo independientes para la reclasificación. El antígeno prostático específico (PSA) inicial, la lateralidad de los cilindros afectos y la densidad de PSA no fueron elementos predictores de progresión en nuestra serie (AU)

Introduction and Objective Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. Materials and Methods Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. Results Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV) ≤ 60cc and the number of positive cylinders > 1 in diagnostic biopsy (p = 0.05) were associated with higher reclassification rate in univariate analysis (p < 0.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, p = 0.04; > 1 positive cylinder at diagnostic biopsy: OR 2.48, p = 0.03). Conclusions It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series (AU)

Una actualización en el protocolo en cáncer de próstata metastásico hormonosensible / Hormone sensitive protocol for metastatic prostate cancer, an update

Revisar y actualizar los últimos protocolos en cáncer de próstata metastásico hormonosensible para mejorar su manejo clínico en la práctica clínica. Realizar un análisis de los datos y los protocolos más recientes en el cáncer de próstata metastásico hormonosensible según paneles de expertos en este ámbito. Actualmente se necesita un grupo de consenso nominal para unificar y mejorar las recomendaciones para el manejo de pacientes sensibles con cáncer de próstata metastásico. Este documento unifica y mejora el manejo de los pacientes con cáncer de próstata metastásico hormonosensible, con una metodología que combina datos cuantitativos y cualitativos, y basada en la participación de un amplio comité científico designado por la Asociación Española de Urología (AU)

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology (AU)

Consenso multidisciplinar sobre idoneidad farmacológica en cáncer de próstata hormono-sensible metastásico / A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer

La terapia de privación androgénica (TPA) es el pilar del tratamiento del cáncer de próstata hormono-sensible metastásico (CPHSm). La adición de docetaxel o de nuevas terapias hormonales (abiraterona, apalutamida o enzalutamida) mejora la supervivencia global (SG) y es en la actualidad el estándar de tratamiento. Sin embargo, la decisión sobre el régimen específico que acompañe a la TPA debe ser discutida con el paciente teniendo en cuenta factores como las posibles toxicidades asociadas, la duración del tratamiento, las comorbilidades o sus preferencias, pues no hay evidencia suficiente para recomendar un régimen sobre otro en la mayoría de los casos. En este trabajo se resume la evidencia sobre el manejo del CPHSm y se aportan recomendaciones consensuadas sobre el tratamiento óptimo para añadir a la TPA en pacientes con CPHSm con especial atención al perfil clínico del paciente (AU)

Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel or new hormone therapies (abiraterone, apalutamide, or enzalutamide) improves overall survival and is currently the standard of care. However, the decision on the specific regimen to accompany ADT should be discussed with the patient, considering factors such as possible associated toxicities, duration of treatment, comorbidities, patient preferences, as there is no sufficient evidence to recommend one regimen over the other in most cases. This paper summarizes the evidence on the management of mHSPC and provides consensus recommendations on the optimal treatment in combination with ADT in mHSPC patients, with special attention to the patient's clinical profile (AU)

Desarrollo e implementación de una unidad de inmunoterapia en un servicio de urología / Development and implementation of an immunotherapy unit in a urology department

Introducción La inmunoterapia está revolucionando el tratamiento del cáncer, siendo los anticuerpos monoclonales dirigidos contra moléculas reguladoras del punto de control la terapia más ampliamente utilizada en la actualidad. Un total de seis fármacos inhibidores del punto de control inmunitario (CPI) han sido aprobados por la U.S. Food and Drug Administration (FDA) y por la European Medicines Agency (EMA) para su uso en diversos tumores sólidos del aparato genitourinario. Material y métodos Se revisó la literatura y se analizó la metodología y experiencia propia adquirida para instaurar el tratamiento con CPI en un servicio de Urología. Resultados Se describen los requisitos recomendables desde el punto de vista formativo, logístico y procedimental para implementar una unidad de inmunoterapia en un servicio de Urología que permita ofrecer con seguridad el tratamiento experto con CPI a los pacientes con tumores genitourinarios. Conclusiones El cumplimiento del programa propuesto garantiza la administración segura de CPI en un entorno hospitalario (AU)

Introduction Immunotherapy is revolutionizing cancer treatment, with monoclonal antibodies directed against checkpoint regulatory molecules currently being the most widely used therapy. A total of six immune checkpoint inhibitor (CPI) drugs have been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in various solid tumors of the genitourinary tract. Material and methods the literature is reviewed and the methodology, as well as our own experience, are analyzed to establish treatment with CPI in a urology department. Results The requirements recommended in terms of training, logistics and procedure are described in order to safely offer expert treatment with CPI to patients with genitourinary tumors. Conclusions Compliance with the proposed program ensures safe administration of immune checkpoint inhibitors in a hospital setting (AU)

A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer.

Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel or new hormone therapies (abiraterone, apalutamide, or enzalutamide) improves overall survival and is currently the standard of care. However, the decision on the specific regimen to accompany ADT should be discussed with the patient, considering factors such as possible associated toxicities, duration of treatment, comorbidities, patient preferences, as there is no sufficient evidence to recommend one regimen over the other in most cases. This paper summarizes the evidence on the management of mHSPC and provides consensus recommendations on the optimal treatment in combination with ADT in mHSPC patients, with special attention to the patient's clinical profile.

Hormone sensitive protocol for metastatic prostate cancer, an update.

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology.

Development and implementation of an immunotherapy unit in a urology department.

INTRODUCTION: Immunotherapy is revolutionizing cancer treatment, with monoclonal antibodies directed against checkpoint regulatory molecules currently being the most widely used therapy. A total of six immune checkpoint inhibitor (CPI) drugs have been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in various solid tumors of the genitourinary tract. MATERIAL AND METHODS: The literature is reviewed and the methodology, as well as our own experience, are analyzed to establish treatment with CPIs in a urology department. RESULTS: The requirements recommended in terms of training, logistics and procedure are described in order to safely offer expert treatment with CPIs to patients with genitourinary tumors. CONCLUSIONS: Compliance with the proposed program ensures safe administration of immune checkpoint inhibitors in a hospital setting.

Cáncer de próstata resistente a la castración no metastásico: recomendaciones de manejo / Non-metastatic castration-resistant prostate cancer: management recommendations

Introducción y objetivo: La supervivencia y calidad de vida (QoL) de los pacientes con cáncer de próstata resistente a la castración no metastásico (CPRCnm) se deteriora de forma muy significativa cuando llegan a desarrollar metástasis. Los antiandrógenos de nueva generación (apalutamida, enzalutamida y darolutamida) pueden prolongar la supervivencia libre de metástasis (SLM) y la supervivencia global (SG) en estos pacientes, manteniendo su QoL.Material y método: Tras una revisión sistemática de la literatura, un comité científico alcanzó un consenso sobre recomendaciones sencillas y prácticas que unifiquen y mejoren el manejo de los pacientes con CPRCnm en las consultas de urología.Resultados: Se dan recomendaciones sobre la frecuencia de determinación de antígeno prostático específico (PSA) y pruebas de imagen en pacientes con CPRCnm. También se destaca la importancia de las comorbilidades en el paciente con CPRCnm y se ofrecen recomendaciones sobre la valoración funcional y de la QoL que se pueden llevar a cabo en la consulta de urología. Se revisa la eficacia, seguridad y efectos sobre la QoL de los antiandrógenos de nueva generación.Conclusiones: Para la evaluación del tratamiento de pacientes con CPRCnm, es necesario tener en cuenta no solo la edad, sino también las comorbilidades y la QoL. Los antiandrógenos de nueva generación son una opción de tratamiento segura y eficaz en los pacientes con CPRCnm. Las recomendaciones de trabajo pueden servir de ayuda para optimizar su manejo de los pacientes con CPRCnm en las consultas de urología. (AU)

Introduction and objective: Survival and quality of life (QoL) of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) deteriorate significantly when they develop metastases. New generation antiandrogens (apalutamide, enzalutamide and darolutamide) can prolong metastasis-free survival (MFS) and overall survival (OS) in these patients, maintaining their QoL.Material and methods: After the performance of a systematic review of the literature, a scientific committee reached a consensus on simple and practical recommendations to consolidate and improve the management of patients with nmCRPC in urology consultations.Results: Recommendations are made on the frequency of PSA determination and imaging tests in patients with nmCRPC. The importance of co-morbidities in patients with nmCRPC is also highlighted, and recommendations are also made on functional and QoL assessment that can be carried out during urology consultations. The efficacy, safety, and effects on QoL of new generation antiandrogens are reviewed.Conclusions: To evaluate treatment of patients with nmCRPC, it is necessary to consider co-morbidities and QoL, in addition to age. New generation antiandrogens are a safe and effective treatment option for patients with nmCRPC. The recommendations of this review can be helpful in optimizing the management of nmCRPC patients in urology consultations. (AU)

Non-metastatic castration-resistant prostate cancer: management recommendations.

INTRODUCTION AND OBJECTIVE: Survival and quality of life (QoL) of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) deteriorate significantly when they develop metastases. New generation antiandrogens (apalutamide, enzalutamide and darolutamide) can prolong metastasis-free survival (MFS) and overall survival (OS) in these patients, maintaining their QoL. MATERIAL AND METHODS: After the performance of a systematic review of the literature, a scientific committee reached a consensus on simple and practical recommendations to consolidate and improve the management of patients with nmCRPC in urology consultations. RESULTS: Recommendations are made on the frequency of PSA determination and imaging tests in patients with nmCRPC. The importance of co-morbidities in patients with nmCRPC is also highlighted, and recommendations are also made on functional and QoL assessment that can be carried out during urology consultations. The efficacy, safety, and effects on QoL of new generation antiandrogens are reviewed. CONCLUSIONS: To evaluate treatment of patients with nmCRPC, it is necessary to consider co-morbidities and QoL, in addition to age. New generation antiandrogens are a safe and effective treatment option for patients with nmCRPC. The recommendations of this review can be helpful in optimizing the management of nmCRPC patients in urology consultations.

Seguridad de nivolumab en pacientes con carcinoma de células renales metastásico: experiencia española en urología en la práctica clínica real / Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting

Introducción y objetivo: Nivolumab es un agente inmunoterapéutico aprobado para el tratamiento de pacientes con carcinoma de células renales (CCR) avanzado tratados previamente. La experiencia en práctica clínica real, especialmente en lo referente a la aparición de reacciones adversas inmunorrelacionadas, es escasa. Presentamos la experiencia acerca de la seguridad de nivolumab en pacientes con CCR metastásico (CCRm) tratados en 9 hospitales de España. Material y métodos: Estudio retrospectivo, multicéntrico en pacientes con CCRm tratados con nivolumab entre 2016 y 2018. Se recogieron datos sociodemográficos y clínicos basales y las reacciones adversas relacionadas con el fármaco. Resultados: Los 26 pacientes incluidos presentaron una edad de 63,7 ± 11,5 años. El 96% presentaba ECOG 0-1 y el 78% un riesgo MKSCC favorable/intermedio. El 73% presentaba subtipo histológico de células claras y el 30%, metástasis de inicio. La mediana de seguimiento fue de 9 meses (rango: 1-14). El 100% de los pacientes presentó una reacción adversa de cualquier grado; las más frecuentes fueron la fatiga, la fiebre y la anemia (27%). El 23% presentó una reacción adversa de grado 3. Las reacciones adversas llevaron a la suspensión del tratamiento en 3 pacientes (11%). Conclusión: En la práctica clínica real, nivolumab presenta un perfil de seguridad favorable y manejable, similar al descrito en otros estudios

Introduction and objectives: Nivolumab is an immunotherapy agent that has been an approved treatment for previously treated patients with advanced renal cell carcinoma (RCC). Experience in real-life settings, especially regarding immune- related adverse events, is scarce. We present our experience with reference to the safety of nivolumab in patients with metastatic RCC (mRCC) treated in 9 hospitals in Spain. Material and methods: Retrospective, multicentre study of patients with mRCC treated with nivolumab between 2016 and 2018. Data on baseline socio-demographic and clinical characteristics and drug-related adverse events were collected. Results: The mean age of the 26 patients included was 63.7 ± 11.5 years; 96% were ECOG 0-1 and 78% had favourable or intermediate MSKCC risk scores; 73% had the clear cell histological subtype and 30% metastatic disease. Median follow-up was 9 months (range 1-14). All patients experienced an adverse event at different grades, with fatigue, fever and anaemia being the most common (27%). Grade 3 adverse events occurred in 23% of patients. Adverse reactions led to treatment suspension in 3 patients (11%). Conclusion: In the real-life clinical setting, nivolumab shows favourable outcomes, similar to those reported by other studies

Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting. / Seguridad de nivolumab en pacientes con carcinoma de células renales metastásico: experiencia española en urología en la práctica clínica real.

INTRODUCTION AND OBJECTIVES: Nivolumab is an immunotherapy agent that has been an approved treatment for previously treated patients with advanced renal cell carcinoma (RCC). Experience in real-life settings, especially regarding immune- related adverse events, is scarce. We present our experience with reference to the safety of nivolumab in patients with metastatic RCC (mRCC) treated in 9 hospitals in Spain. MATERIAL AND METHODS: Retrospective, multicentre study of patients with mRCC treated with nivolumab between 2016 and 2018. Data on baseline socio-demographic and clinical characteristics and drug-related adverse events were collected. RESULTS: The mean age of the 26 patients included was 63.7±11.5 years; 96% were ECOG 0-1 and 78% had favourable or intermediate MSKCC risk scores; 73% had the clear cell histological subtype and 30% metastatic disease. Median follow-up was 9 months (range 1-14). All patients experienced an adverse event at different grades, with fatigue, fever and anaemia being the most common (27%). Grade 3 adverse events occurred in 23% of patients. Adverse reactions led to treatment suspension in 3 patients (11%). CONCLUSION: In the real-life clinical setting, nivolumab shows favourable outcomes, similar to those reported by other studies.

Pseudoaneurisma de arteria renal tras nefrectomía parcial laparoscópica. Diagnóstico, tratamiento y revisión bibliográfica / Renal artery pseudoaneurysm after partial nephrectomy. Diagnosis, treatment and literature review

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[Malignant fibrous histiocytoma of the bladder. A literature review]. / Histiocitoma fibroso maligno de vejiga. Revisión bibliográfica.

OBJECTIVES: Malignant fibrous histiocytoma (MFH) is an uncommon urinary tract tumor. This paper is intended to provide an update on its diagnostic criteria, pathological and immunohistochemical characteristics, histological classification, prognostic factors, and alternative treatments. MATERIALS AND METHODS: All published articles on MFH of the urinary bladder have been reviewed and a descriptive study has been done. RESULTS: Twenty-nine cases of MFH of the bladder have been reported. The most common morphological variants are storiform-fascicular (41%) and inflammatory (36%) MFH. Non-myxoid variants have a poorer prognosis. Stage T3 MFH was found in 72% of cases at the time of diagnosis. MFH local recurrence and distant metastasis rates were 50% and 25% respectively after surgical treatment only. CONCLUSIONS: MFH of the bladder is a tumor with high local and distant recurrence rates and a low survival rate, and therefore requires early and aggressive treatment. Radical cystectomy with lymphadenectomy and adjuvant radiotherapy is considered to be the treatment of choice, eventually associated to chemotherapy.

Histiocitoma fibroso maligno de vejiga. Revisión bibliográfica / Malignant fibrous histiocytoma of the bladder. A literature review

Objetivos: El histiocitoma fibroso maligno (HFM) es un tumor poco frecuente del tracto urinario. Pretendemos actualizar los criterios diagnósticos, las características anatomopatológicas e inmunohistoquímicas, la clasificación histológica, los factores pronóstico y las alternativas terapéuticas. Material y métodos: Revisión bibliográfica y estudio descriptivo de los casos de HFM de vejiga publicados en la literatura médica internacional. Resultados: Existen 29 casos publicados de HFM de vejiga y las variantes morfológicas más frecuentes son la estoriforme-fascicular (41%) y la inflamatoria (36%). Las variantes no mixoides comportan peor pronóstico. El 72% fue T3 en el momento del diagnóstico. La tasa de recurrencia local y a distancia del HFM de vejiga fue del 50 y del 25%, respectivamente, tras tratamiento exclusivamente quirúrgico. Conclusiones: El HFM de vejiga es un tumor con alta tasa de recurrencia local y a distancia, así como baja supervivencia, requiriendo un tratamiento precoz y agresivo. La cistectomía radical con linfadenectomía y radioterapia adyuvante, con eventual quimioterapia, se considera el tratamiento de elección (AU)

Objectives: Malignant fibrous histiocytoma (MFH) is an uncommon urinary tract tumor. This paper is intended to provide an update on its diagnostic criteria, pathological and immunohistochemical characteristics, histological classification, prognostic factors, and alternative treatments. Materials and methods: All published articles on MFH of the urinary bladder have been reviewed and a descriptive study has been done. Results: Twenty-nine cases of MFH of the bladder have been reported. The most common morphological variants are storiform-fascicular (41%) and inflammatory (36%) MFH. Non-myxoid variants have a poorer prognosis. Stage T3 MFH was found in 72% of cases at the time of diagnosis. MFH local recurrence and distant metastasis rates were 50% and 25% respectively after surgical treatment only. Conclusions: MFH of the bladder is a tumor with high local and distant recurrence rates and a low survival rate, and therefore requires early and aggressive treatment. Radical cystectomy with lymphadenectomy and adjuvant radiotherapy is considered to be the treatment of choice, eventually associated to chemotherapy (AU)

[Genetic study of six chromophobic renal carcinomas]. / Estudio genético de 6 carcinomas renales cromófobos.

OBJECTIVES: To determine the role of tumor suppressor genes p53 and von Hippel-Lindau (VHL), and the specific loss of chromosomes 1, 2, 3, 6, 10, 13, 17 and 21 in the pathogenesis of Chromophobe Renal Cell Carcinomas (CrRCC). MATERIAL & METHODS: Renal tumor specimens and normal kidney tissue from 6 patients affected of CrRCC were obtained after radical nephrectomy and immediately snap-frozen. PCR-SSCP analysis for mutations of p53 (exons 5-8) and VHL genes was performed in all cases. All of the positive cases in SSCP analysis were further characterized by direct sequencing. Inactivation by VHL methylation were searched by Southern blot analysis. Microsatellite analysis using several markers covering both arms of chromosomes 1, 2, 6, 10, 13 and 17, as well as 3p and 21q, was performed to investigate specific loss of these chromosomes. RESULTS: Mutations of p53 were detected in 2 (33%) of the 6 CrRCCs, showing both tumors loss of heterocigosity (LOH) on 17p. VHL mutations and inactivation by methylation were not detected in any tumor. In 5 (83.3%) of the 6 CrRCCs, microsatellite analysis showed LOH at every informative marker on all the regions tested except 3p. Retention of heterozigosity on 3p was present in all cases. CONCLUSIONS: Mutations of p53 in CrRCCs are more frequent (33% in our series) than in clear cell renal cell carcinomas (< 2% in most series). Despite 65-75% of clear cell RCCs show VHL mutations (60%) and inactivation by methylation (5-20%), no CrRCC in our series showed these alterations. LOH in the specific chromosomes tested (1, 2, 6, 10, 13, 17 and 21) confirm cytogenetic findings that characterize CrRCCs (specific combinations of multiple chromosomal losses). Our results, similar to those reported by other authors, confirm that CrRCC is not only a histologic fenotype, but also a distinctive genotype from other RCCs. The specific combination of chromosomal losses allows a quick and easy diagnostic of this kind of neoplasms with a simple technique of microsatellite analysis.

Análisis de microsatélites de la región 3p13-p25 en el carcinoma de células renales en humanos / Microsatellite analysis of the 3p13-p25 regions in renal cell carcinoma in humans

INTRODUCCIÓN Y OBJETIVOS: En el desarrollo del carcinoma de células renales no papilar (Carcinoma Renal Convencional-CRC) se han implicado deleciones terminales e intersticiales de diversas regiones del 3p. Se ha realizado un análisis de microsatélites en la región 3p13-p25 para estudiar el papel del brazo corto del cromosoma 3 en la patogénesis del Carcinoma de Células Renales (CCR).MATERIAL Y MÉT ODOS: Se obtuvieron muestras de las piezas de nefrectomía de 57 pacientes afectos de tumor renal. Los controles normales de DNA constitucional lo constituyeron las muestras de riñón sano y sangre periférica de cada paciente. La valoración de la pérdida de heterocigosidad (LOH) se determinó mediante 8 marcadores localizados en 3p13-p25. Las alteraciones genéticas se han correlacionado con la histología, grado nuclear, estadio patológico e infiltración celular estromal.RESULTADOS: Un total de 41 casos (71,9 por ciento) correspondieron a carcinomas renales de células claras o convencionales (CRC), 7 (12,3 por ciento) carcinomas cromófobos, 5 (8.8 por ciento) carcinomas papilares, y 4 (7 por ciento) oncocitomas. El 73.2 por ciento de los CRC mostró LOH, pero ninguno de los restantes tipos histológicos. Deleciones terminales se detectaron en 53,3 por ciento de los CRC con LOH, y el resto mostraron deleciones intersticiales múltiples (46,6 por ciento). La región 3p14.2 presenta una región común de pérdida. Debido a la contaminación con ADN normal, cuando la infiltración celular estromal aumenta. se detectan menor número de LOH. No se ha encontrado asociación de LOH 3p con el grado nuclear, ni con el estadio patológico.CONCLUSIONES: 1. El análisis de microsatélites de LOH en 3p puede ser utilizado para el diagnóstico diferencial de los tumores renales. 2. La evidencia de múltiples deleciones intersticiales en un gran número de CRC sugiere que más de un gen debe estar implicado eu la génesis de esta neoplasia, y que ya debe estar presente en estadios tempranos de la oncogénesis. 3. La región común de pérdida 3p14.2 sugiere la presencia de secuencias inestables de ADN que juegan un papel importante en la patogénesis del CRC. 4. LOH en 3p en la mayoría de los CRC, independientemente del grado y estadio. demuestra que estas alteraciones moleculares no marcan un comportamiento más agresivo del tumor. (AU)