Pigmentation phototype and prostate and breast cancer in a select Spanish population-A Mendelian randomization analysis in the MCC-Spain study.

INTRODUCTION: Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. METHODS: We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype-cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. RESULTS: The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. CONCLUSIONS: Phototype is not associated with breast or prostate cancer.

Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: a mechanism-based epidemiological study.

BACKGROUND: Previous evidence suggests that 25-hydroxyvitamin D(3) [25(OH)D(3)] protects against several cancers. However, little is known regarding urothelial bladder cancer (UBC). We analyzed the association between plasma 25(OH)D(3) and overall risk of UBC, as well as according to stage and FGFR3 molecular subphenotypes. METHODS: Plasma concentrations of 25(OH)D(3) in 1125 cases with UBC and 1028 control subjects were determined by a chemiluminescence immunoassay. FGFR3 mutational status and expression in tumor tissue were assessed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusting for potential confounders. Analyses were further stratified by tumor invasiveness and grade, FGFR3 expression, and smoking status. Cell proliferation was measured in human UBC cell lines cultured with 1α,25-dihydroxyvitamin D(3). RESULTS: A statistically significantly increased risk of UBC was observed among subjects presenting the lowest concentrations of 25(OH)D(3) (OR(adj) = 1.83; 95% CI = 1.19 to 2.82; P = .006), showing a dose-response effect (P (trend) = .004). The association was stronger for patients with muscle-invasive tumors, especially among low-FGFR3 expressers (OR(adj) = 5.94; 95% CI = 1.72 to 20.45; P = .005). The biological plausibility of these associations is supported by the fact that, in vitro, 1α,25-dihydroxyvitamin D(3) upregulates FGFR3 expression in UBC cell lines with low levels of wild-type FGFR3. CONCLUSION: These findings support a role of vitamin D in the pathogenesis of UBC and show that 25(OH)D(3) levels are associated with FGFR3 expression in the tumor. Because FGFR3 mutation and overexpression are markers of better outcome, our findings suggest that individuals with low levels of plasma 25(OH)D(3) may be at high risk of more aggressive forms of UBC.

Expression of matrix metalloproteinase-9 in prostate cancer. Preliminary experience.

OBJECTIVES: To study the validity of Matrix Metalloproteinase 9 as a complementary marker to PSA for the diagnosis and prognosis of Prostate Cancer. METHODS: Prospective study structured as a hospital-based cohort of 100 consecutive patients undergoing prostate biopsy. Serum determination of MMP-9 was carried out by means of inmunoassay. Statistical analysis was performed using the Stata/SE 8.2 software. RESULTS: 32 patients were diagnosed with prostate cancer and 52% had a Gleason score equal to or greater than 7. The values of serum MMP-9 varied between 225.7 and 1932.3 ng/ml, without significant differences among patients with benign, malignant and uncertain histology (p=0.429). The differences approached statistical significance in the subgroup of patients with PSA at 4-10 ng/ml (p=0.058), and significant differences were observed in the subgroup with free PSA to total PSA coefficient of less than 15% (p=0.037). No relationship between the Gleason score and the level of MMP-9 was shown (p=0.739). The levels of PSA and MMP-9 were shown to be independent (Pearson coefficient of correlation -0.1). CONCLUSIONS: It was not possible to show the efficacy of MMP-9 in predicting the result of the biopsy. In the group of patients with slightly increased levels of PSA (between 4 and 10 ng/ml) all the descriptive variables were higher in the group with malignant histology, though they did not reach statistical significance, they did reach significance when the coefficient of free PSA over total PSA was less than 15%, but this finding is not relevant clinically, as these patients already have a clear indication for biopsy. Neither was the relationship with the prognosis shown as there are no differences of MMP-9 expression at varying Gleason scores.

Matrix metalloproteinase- 9 polymorphisms in the diagnosis of prostate cancer. A preliminary experience.

UNLABELLED: Polymorphisms Q279R, P574R and -1562 C/T of matrix metalloproteinase-9 (MMP-9) gene have been linked with the risk of cancer and with tumoral aggressiveness in various types of cancer. So far there are no studies in the literature analysing the link between polymorphisms Q279R, P574R and -1562 C/T of MMP-9 and prostate cancer. OBJECTIVES: To establish the presence of the MMP-9's gene polymorphisms (Q279R, P574R and -1562 C/T)in relation to results of prostate biopsy, PSA values and Gleason score. METHODS: Hospital cohort of 100 patients with suspected prostate cancer, subjected to prostate biopsy, in whom the MMP-9 polymorphisms (Q279R, P574R and -1562 C/T) were analysed using the PCR-RLFP technique. RESULTS: No statistically significant differences were found in the presence of the Q279R, P574R and -1562 C/T polymorphisms in terms of prostate biopsy results (p = 0.264, p = 0.406, p = 0.860, respectively), or Gleason score (p = 0.373, p = 0.367, p = 0.476). Comparing the genotypes of the Q279R, P574R and -1562 C/T polymorphisms resulting from prostate biopsy, using subgroups according to PSA values, no statistically significant differences were found either (p = 0.332 y p = 0.393, respectively ). However, statistically significant differences were found when comparing the genotypes of the -1562 C/T polymorphism of the MMP-9 in patients showing positive biopsy for malignant tumour in comparison to a negative biopsy for a malignant tumour in the subgroup of patients with PSA 10 ng/ml (p=0.049). The joint analysis of the three MMP-9 polymorphisms, using logistical regression study did not reveal any statistically significant differences as far as the risk of developing prostate cancer is concerned based on the presence of the Q279R, P574R and -1562 C/T polymorphisms. CONCLUSION: The Q279R, P574R and -1562 C/T polymorphisms are not linked with the aggressiveness in prostate cancer, neither they are linked to the risk of suffering prostate cancer.

Expresión de metaloproteasa de matriz 9 en el cáncer de próstata. Experiencia preliminar / Expression of matrix metalloproteinase-9 in prostate cancer. Preliminary experience

OBJETIVO: Estudiar la validez de la metaloproteasa 9 (MMP-9) como marcador complementario al PSA en el diagnóstico y el pronóstico del carcinoma de próstata.MÉTODO: Estudio prospectivo estructurado como cohorte de base hospitalaria. Fueron incluidos 100 pacientes consecutivos a los que se iba a practicar una biopsia prostática. La determinación sérica de MMP-9 se realizó mediante inmunoensayo, y el análisis estadístico con el programa informático stata/SE 8.2.RESULTADOS: 32 pacientes fueron diagnosticados de carcinoma prostático y el 52% de ellos con grado Gleason mayor o igual a 7. Los valores de MMP-9 sérica oscilaron entre 225,7 y 1932,3 nanogramos por mililitro, sin encontrar diferencias estadísticamente significativas entre los pacientes con histología benigna, maligna e incierta (p=0,429). Las diferencias se acercaron a la significación estadística en el subgrupo de pacientes con PSA 4-10 ng/ml (p=0,058) y en el subgrupo PSA libre/total menor de 15% se observaron diferencias significativas (p=0,037). No se encontró relación entre el grado Gleason y el nivel de MMP-9 (p=0,739). Los niveles de PSA y MMP-9 demostraron ser independientes (Coeficiente de correlación de Pearson -0,1).CONCLUSIONES: No fue posible demostrar la eficacia de la MMP-9 para predecir el resultado de la biopsia. En el grupo de pacientes con elevaciones discretas del PSA (entre 4 y 10 ng/ml) todas las variables descriptivas fueron superiores en el grupo con histología maligna, sin alcanzar la significación estadística. Sí se alcanzó la significación cuando el cociente de PSA libre entre PSA total fue menor del 15%, pero este hallazgo no tiene relevancia en la práctica clínica, pues estos pacientes ya tienen indicación clara de biopsia. Tampoco se demuestra relación con el pronóstico al no existir diferencias de expresión de MMP-9 entre diferentes grados Gleason(AU)

OBJECTIVES: To study the validity of Matrix Metalloproteinase 9 as a complementary marker to PSA for the diagnosis and prognosis of Prostate Cancer.METHODS: Prospective study structured as a hospital-based cohort of 100 consecutive patients undergoing prostate biopsy. Serum determination of MMP-9 was carried out by means of inmunoassay . Statistical analysis was performed using the Stata/SE 8.2 software.RESULTS: 32 patients were diagnosed with prostate cancer and 52% had a Gleason score equal to or greater than 7. The values of serum MMP-9 varied between 225.7 and 1932.3 ng/ml, without significant differences among patients with benign, malignant and uncertain histology (p=0.429). The differences approached statistical significance in the subgroup of patients with PSA at 4-10 ng/ml (p=0.058), and significant differences were observed in the subgroup with free PSA to total PSA coefficient of less than 15% (p=0.037). No relationship between the Gleason score and the level of MMP-9 was shown (p=0.739). The levels of PSA and MMP-9 were shown to be independent (Pearson coefficient of correlation -0.1).CONCLUSIONS: It was not possible to show the efficacy of MMP-9 in predicting the result of the biopsy. In the group of patients with slightly increased levels of PSA (between 4 and 10 ng/ml) all the descriptive variables were higher in the group with malignant histology, though they did not reach statistical significance, they did reach significance when the coefficient of free PSA over total PSA was less than 15%, but this finding is not relevant clinically, as these patients already have a clear indication for biopsy. Neither was the relationship with the prognosis shown as there are no differences of MMP-9 expression at varying Gleason scores(AU)

Polimorfismo de la metaloproteasa de matriz 9 (MMO-9) en el diagnostico del carcinoma prostático. Experiencia preliminar / Matrix metalloproteinase 9 polyphormisms in the diagnosis of prostate cancer. A preliminary experience

Los polimorfismos Q279R, P574R y -1562 C/T en el gen de la MMP-9 se han relacionado con el riesgo de padecer cáncer y con la agresividad tumoral de varios tipos de cánceres. Hasta ahora no existen estudios en la literatura que analicen la asociación de los polimorfismos Q279R, P574R y -1562 C/T de la MMP-9 con el cáncer prostático.OBJETIVOS: Determinar las diferencias de presencia de los polimorfismos en el gen de la MMP-9 (Q279R, P574R y -1562 C/T) en función del resultado de la biopsia prostática, de las cifras del PSA y el grado histológico Gleason.MÉTODOS: Se trata de una cohorte de base hospitalaria que incluye 100 pacientes con sospecha de carcinoma prostático, sometidos a biopsia prostática, a los que se determinaron los polimorfismos de la MMP-9 (Q279R, P574R y -1562 C/T) mediante la técnica de PCR-RFLP.RESULTADOS: No se encontraron diferencias estadísticamente significativas en la presencia de los polimorfismos Q279R, P574R y -1562 C/T de la MMP-9, en función del resultado de la biopsia prostática (p = 0,264, p = 0,406, p = 0,860, respectivamente), ni en función del grado Gleason (p = 0,373, p = 0,367, p = 0,476). Al comparar los distintos genotipos de los polimorfismos Q279R y P574R de la MMP-9 en función del resultado de la biopsia prostática, haciendo subgrupos según las cifras del PSA, tampoco se encontraron diferencias estadísticamente significativas (p = 0,332 y p = 0,393, respectivamente). Se encontraron diferencias estadísticamente significativas al comparar los distintos genotipos del polimorfismo -1562 C/T de la MMP-9, en pacientes con biopsia positiva para tumor maligno respecto a biopsia negativa para tumor maligno en el subgrupo de pacientes de PSA > 10 ng/ml (p = 0,049)...(AU)

Polymorphisms Q279R, P574R and -1562 C/T of matrix metalloproteinase-9 (MMP-9) gene have been linked with the risk of cancer and with tumoral aggressiveness in various types of cancer. So far there are no studies in the literature analysing the link between polymorphisms Q279R, P574R and -1562 C/T of MMP-9 and prostate cancer.OBJECTIVES: To establish the presence of the MMP-9´s gene polymorphisms (Q279R, P574R and -1562 C/T)in relation to results of prostate biopsy, PSA values and Gleason score.METHODS: Hospital cohort of 100 patients with suspected prostate cancer, subjected to prostate biopsy, in whom the MMP-9 polymorphisms (Q279R, P574R and -1562 C/T) were analysed using the PCR-RLFP technique.RESULTS: No statistically significant differences were found in the presence of the Q279R, P574R and -1562 C/T polymorphisms in terms of prostate biopsy results (p = 0.264, p = 0.406, p = 0.860, respectively), or Gleason score (p = 0.373, p = 0.367, p = 0.476). Comparing the genotypes of the Q279R, P574R and -1562 C/T polymorphisms resulting from prostate biopsy, , using subgroups according to PSA values, no statistically significant differences were found either (p = 0.332 y p = 0.393, respectively ). However, statistically significant differences were found when comparing the genotypes of the -1562 C/T polymorphism of the MMP-9 in patients showing positive biopsy for malignant tumour in comparison to a negative biopsy for a malignant tumour in the subgroup of patients with PSA > 10 ng/ml (p=0.049). The joint analysis of the three MMP-9 polymorphisms, using logistical regression study did not reveal any statistically significant differences as far as the risk of developing prostate cancer is concerned based on the presence of the Q279R, P574R and -1562 C/T polymorphisms.CONCLUSION: The Q279R, P574R and -1562 C/T polymorphisms are not linked with the aggressiveness in prostate cancer, neither they are linked to the risk of suffering prostate cancer(AU)

[Advantages and risks of the use of prostate-specific antigen (PSA) in the health-care area No. 4 of Gijon (Asturias)]. / Ventajas y riesgos de la utilización del antígeno prostático específico (PSA) en el area sanitaria v de Gijón (Asturias).

OBJECTIVES: The diagnosis of prostate cancer has changed significantly with the introduction of PSA in the clinical practice. Despite screening is under controversy the use of PSA has become widespread. The objective of this paper is to know the use of PSA in our health-care area and to analyze perceived risks and benefits. METHODS: From the informatic archives we analyze PSA determinations performed in our health-care area (290.956 citizens) over 2000 and 2001. We also analyzed prostate biopsies generated and number of cancers detected. RESULTS: 25.519 PSA determinations were performed. 59% came from general practitioners (GP), 34% from urologists and 7% from the rest of specialists. 39% are performed to men older than 70 years. PSA was normal in 78.7% of the patients and higher than 4 ng/ml in 21.2%. 488 prostatic biopsies were performed diagnosing 178 cancers (diagnostic yield 36.5%). Depending on the first PSA, diagnosis was started by a GP in 44% of the cases, a urologist in 46%, and the remaining 10% by other specialists. Mean time from first PSA to diagnosis was 5 months, without significant differences between GPs and specialities . The use of PSA by GPs is variable (between 8.1 and 45.8 determinations per 100 men over 50 years), without significant differences in prostate cancer detection by number of PSAs or differences in age. In comparison with the period 1982-1993 the incidence of prostate cancer goes from 30.76 to 52.8 new cases/100.000 inhabitants/year. There is a greater incidence and increase of cancer in the rural area (from 33.52 to 221.1 new cases/ 100.000 inhabitants/year). CONCLUSIONS: We confirm the general use of this test and the trend to screening in the primary health-care level, which participates in an important manner in the diagnosis. PSA brings forward the diagnosis of prostate cancer 5 years in our area, and shoots its incidence rates. The high use of such marker in our population of advanced age may be considered inadequate.

Ventajas y riesgos de la utilización del antígeno prostático específico (PSA) en el área sanitaria V de Gijón (Asturias) / Advantages and risk´s of the use of PSA in the health-care area Nº. 5 of Gijon (Asturias)

OBJETIVO: Con la introducción del PSAen la práctica clínica diaria, el diagnóstico del cáncerde próstata ha sufrido importantes cambios. Aunque elscreening es controvertido, su uso parece que se hageneralizado. Conocer la utilización que se hace delPSA en nuestro área sanitaria y analizar los beneficiosy riesgos que se perciben.MÉTODO: A través del archivo informático, analizamoslas determinaciones realizadas durante los años2000 y 2001 en nuestro área (290.956 habitantes).Se analizaron también las biopsias de próstata generadasy los cánceres detectados.RESULTADOS: Se realizaron 25.590 determinacionesde PSA. Proceden de Atención Primaria 59%, Urología34% y resto de especializada 7%. El 39% se realizana hombres mayores de 70 años. El PSA fue normal enel 78,7%, y mayor de 4 ng/mL en 21,2%. Se realizaron488 biopsias prostáticas, detectándose 178 carcinomas(36,5% rendimiento diagnóstico). Según el primerPSA el diagnóstico parte de primaria en 44%,Urología en 46% y resto de especializada 10%. Eltiempo medio desde el primer PSA hasta el diagnósticofue de 5 meses, sin diferencias significativas entrePrimaria y Especializada. El uso del PSA por Primariaes variable (entre 8,1 y 45,8 determinaciones porcada 100 hombres mayores de 50 años), sin diferenciassignificativas de detección de cáncer prostáticosegún número de PSAs ni diferencias de edad. Frenteal periodo 1982-1993 la incidencia de cáncer prostáticopasa de 30,76 a 52,8 nuevos casos/ 100.000habitantes/ año. Existe mayor incidencia e incrementodel cáncer en la zona rural (de 33,52 a 221,1 nuevoscasos/ 100.000 habitantes/ años).CONCLUSIONES: Confirmamos la utilización generalizadade esta prueba y la tendencia al cribado en primaria,que participa de manera importante en el diagnóstico.El PSA adelanta el diagnóstico del cáncer depróstata en 5 años en nuestro área, y dispara las tasasde incidencia de este cáncer. La elevada utilización deeste marcador en población de edad avanzada sepuede considerar inadecuada

OBJECTIVES: The diagnosis of prostatecancer has changed significantly with the introductionof PSA in the clinical practice. Despite screening isunder controversy the use of PSA has become widespread.The objective of this paper is to know the use of PSA inour health-care area and to analyze perceived risks andbenefits.METHODS: From the informatic archives we analyzePSA determinations performed in our health-care area(290.956 citizens) over 2000 and 2001. We alsoanalyzed prostate biopsies generated and number ofcancers detected.RESULTS: 25.519 PSA determinations were performed.59% came from general practitioners (GP), 34% fromurologists and 7% from the rest of specialists. 39% areperformed to men older than 70 years. PSA was normalin 78.7% of the patients and higher than 4 ng/ml in21.2%. 488 prostatic biopsies were performeddiagnosing 178 cancers (diagnostic yield 36.5%).Depending on the first PSA, diagnosis was started by aGP in 44% of the cases, a urologist in 46%, and theremaining 10% by other specialists. Mean time fromfirst PSA to diagnosis was 5 months, without significantdifferences between GPs and specialities . The use ofPSA by GPs is variable (between 8 .1 and 45.8determinations per 100 men over 50 years), withoutsignificant differences in prostate cancer detection bynumber of PSAs or differences in age. In comparisonwith the period 1982-1993 the incidence of prostatecancer goes from 30.76 to 52.8 new cases/100.000inhabitants/year. There is a greater incidence andincrease of cancer in the rural area (from 33.52 to221.1 new cases/100.000 inhabitants/year).CONCLUSIONS: We confirm the general use of thistest and the trend to screening in the primary health-carelevel, which participates in an important manner in thediagnosis. PSA brings forward the diagnosis of prostatecancer 5 years in our area, and shoots its incidencerates. The high use of such marker in our population ofadvanced age may be considered inadequate

[Neuroblastoma in adolescence. Report of a new case]. / Neuroblastoma en la adolescencia. Aportación de un nuevo caso.

OBJECTIVE: To report an uncommon case of neuroblastoma in adolescence. METHODS: A case of neuroblastoma in adolescence is presented. The etiological and pathogenetic factors, clinical and laboratory findings, behavior and treatments are discussed. RESULTS/CONCLUSIONS: Neuroblastoma and related tumors, ganglioneuroblastoma and ganglioneuroma are derived from primordial neural crest cells that migrate in the embrionary period and populate the primordial sympathetic ganglia and adrenal medulla. Neuroblastoma, the least differentiated, resembles the fetal adrenal medulla. The peak age at the time of presentation is about 18 months and only sporadic cases occur during adolescence, as the case described herein, or adult life.

Nuestra experiencia en adrenalectomías (1994-2000). Revisión de conjunto / Our experience with adrenalectonomy. A review of our series from 1994-2000

OBJETIVO: Presentamos 30 casos de adrenalectomía por masa suprarrenal, realizados en nuestro servicio en los últimos 6 años. MÉTODO: Un tercio de los pacientes fueron mujeres. La edad osciló entre 16 y 83 años con media de 51. En relación a la clínica presentada, el 18,5 por ciento fue un hallazgo casual, presentaron dolor abdominal o lumbar el 33,3 por ciento, síndrome de Cushing en el 18,5 por ciento,cefaleas y HTA el 18,5 por ciento, virilización y un paciente presentó clínica derivada de la hipocaliemía. Los métodos de diagnóstico básico utilizados fueron: estudios de funcionalidad, ecografía y TAC realizándose gammagrafía con MIBG, RNM o arteriografía en casos concretos. La incisión más habitual fue la lumbotomía en el 53 por ciento de las intervenciones. RESULTADOS: El postoperatorio osciló entre 7 y 23 días con una media de 11. Las complicaciones derivadas de la intervención aparecieron en el 38,4 por ciento de los pacientes intervenidos: esplenectomía, reintervención por sangrado, problemas derivados del control tensional, problemas vasculares (TIA,TVP), infección de herida quirúrgica y neumonía. El 50 por ciento de las masas resultaron feocromocitomas, el 10 por ciento carcinomas y el 5 por ciento adenomas. En el resto nos encontramos con tumores de la cresta neural, un quiste adrenal calcificado, un mielolipoma y una metástasis de primario renal CONCLUSIONES: Realizamos una revisión de los aspectos diagnósticos y terapéuticos de las masas suprarrenales (AU)

Análisis de ploidía de ADN y fases del ciclo celular por citometría de flujo en el lavado vesical. Experiencia preliminar / Analysis of DNA ploidy and cell phase fractions by bladder wash flow cytometry: Preliminary result

OBJETIVO: Estimación pronóstica en el carcinoma vesical del análisis de ploidía de ADN y fases del ciclo celular por citometría de flujo en el lavado vesical. MÉTODOS: Obtención de muestras por lavado vesical de 25 pacientes, 16 previa a la intervención del tumor y 9 durante la cistoscopia de seguimiento. Tinción con Ioduro de propidio y análisis en un citómetro FacScan de Becton Díckinson. El análisis del ciclo celular se realizó mediante el programa Cellfit versión 2.01 de Becton Dickinson. RESULTADOS: El rendimiento celular fue suficiente para el análisis citométrico en todos los casos. En las 13 muestras tumorales (8 tumores superficiales y 5 infiltrantes), se detectaron aneuploidías en 3 casos, presentando peor pronóstico: el único tumor superficial en el que se detectó una población aneuploide, recidivó a los 15 meses después de la intervención; de los 5 tumores infiltrantes, los dos que presentaban aneuploidías fallecieron por desarrollo de metástasis antes de los 6 meses. En cuanto a la fracción de fase S, en los pacientes sin tumor macroscópico se detectó un único caso de aumento de este porcentaje (19,5 por ciento de células en fase S); a este paciente se le detectó una recidiva tumoral 6 meses después del análisis. En el grupo de pacientes con tumor el análisis de la fracción de fase S no resultó significativa para el pronóstico. CONCLUSIONES: El análisis de ploidía de ADN y fases del ciclo celular por citometría de flujo en el lavado vesical pueden incrementar la capacidad pronóstico en el carcinoma vesical: las aneuploidías se asocia con peor pronóstico y un aumento de la fracción de fase S puede predecir la recidiva tumoral meses antes de su aparición clínica (AU)