RESUMEN
BACKGROUND: We assessed the predictive value of TP53 mutations and prostate-specific antigen (PSA) for tumor progression in prostate cancer (PCa) patients. MATERIALS AND METHODS: Ninety tumor tissue samples of patients with PCa from radical prostatectomy were used. Tumor progression was estimated biochemically by the PSA level (> 0.2 microg/l) or by detection of metastases. Screening for TP53 mutations was performed by temperature gradient gel electrophoresis (TGGE) in exon-specific manner. Follow-up data were collected from medical protocols. Statistical analysis was performed by uni- and multivariate techniques. RESULTS: In 32 out of 90 patients (35.6%), TP53 mutations were detected. Thirteen out of 32 patients (40.6%) with TP53 mutations and nine out of 58 patients (15.5%) with TP53 wild-type showed tumor progression after 25 and 45 months, respectively. CONCLUSION: TP53 mutations in exon 7 and exon 8 are factors of tumor progression in PCa. Their contribution to tumor recurrence is more significant than tumor stage and pretherapeutic PSA level.
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Genes p53 , Mutación , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Análisis Mutacional de ADN , Progresión de la Enfermedad , Exones , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Antígeno Prostático Específico/química , Prostatectomía/métodos , Factores de Riesgo , TemperaturaRESUMEN
Partial segmental thrombosis of the corpus cavernosum is a rare disease of unknown etiology; the thrombosis is always located in the proximal part of the corpus cavernosum, usually unilaterally. Typical clinical presentation with perineal pain and swelling in combination with cross-sectional imaging allows one to confidentially establish this diagnosis.
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Diagnóstico por Imagen/métodos , Enfermedades del Pene/diagnóstico , Pene/irrigación sanguínea , Trombosis/diagnóstico , Adulto , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Dolor Pélvico/diagnóstico , Dolor Pélvico/etiología , Enfermedades del Pene/tratamiento farmacológico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Terapia Trombolítica/métodos , Trombosis/tratamiento farmacológico , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Ultrasonografía DopplerRESUMEN
This study evaluates the influence of the TP53 genetic status on tumour recurrence and progression with a highly effective electrophoretic technique. DNA from tissue of 75 non-invasive urinary bladder cancers was PCR amplified in the TP53 exons 5-8 and run on horizontal polyacrylamide gels under defined temperature conditions to yield specific gel shifts. Kaplan-Meier and Cox-Regression analysis were performed with tumour progression. The overall tumour recurrence in our patient population was 76.0% (57/75). Tumour recurrence frequency was 69.4% (34/49) in patients with TP53 wild-type, and 88.5% (23/26) in patients with TP53 mutation. There was no statistically significant difference with regard to recurrence frequency and time to recurrence. The progression-free survival was significantly shorter in patients with TP53 mutations, and the frequency of tumour progression was significantly higher in mutated as compared to wild-type tumours. Cox-Regression analysis showed a significant and independent influence of TP53 mutation on tumour progression in comparison with tumour grade, stage and history of prior bladder cancer. If segregated by exons, mutations in the DNA binding region of exon 8 seem to have a particular high influence on tumour progression. We conclude that genetic analysis of TP53 can select patients at high risk of bladder tumour progression that should be followed closely and may benefit from early radical surgical procedures.
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Biomarcadores de Tumor/genética , Genes p53 , Mutación , Neoplasias de la Vejiga Urinaria , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: Obesity is estimated to account for up to 20% of all cancer deaths. Mutations of TP53 are frequently correlated with tumor development and progression. We evaluated the effect of body mass index (BMI) and mutation status of tumor suppressor gene p53 (TP53) on patients with urinary bladder cancer. MATERIALS AND METHODS: Clinical samples were used from 75 patients with tumors of the urinary bladder. Mutation status in TP53 exons 5, 6, 7, and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included Pearson's correlation. RESULTS: For noninvasive bladder cancer, the mutation frequency in TP53 was 44.6%, while for invasive bladder cancer the mutation frequency in TP53 was 84.2%. Normal weight, overweight, and patients with obesity had a TP53 mutation frequency of 68.4%, 44.8%, and 25%, respectively (P < 0.05). CONCLUSIONS: TP53 mutation frequently occurs in higher stages of bladder tumors. Body mass index is not associated with a higher TP53 mutation frequency in our study, but BMI should be included for collecting data of bladder cancer risk profile.
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Índice de Masa Corporal , Obesidad/complicaciones , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/genética , Anciano , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: The predictive value of TP53 mutations and prostate-specific antigen (PSA) was assessed in prostate needle biopsies of samples without signs of malignancy for later affliction by prostate cancer (PCa). Comparison of mutation frequency and PSA level in prostate needle biopsies with data of patients with benign prostate hyperplasia (BPH) treated by transurethral resection (TURP), patients with prostatic intraepithelial neoplasia (PIN), and patients with PCa, was made. MATERIALS AND METHODS: A total of 466 samples were analysed from patients with benign and malignant diseases of the prostate, including 52 samples of needle biopsies of the prostate with repeated benign histopathological diagnosis. Analysis of TP53 state by temperature gradient gel electrophoresis of TP53 exon-specific PCR products of exons 5, 6, 7 and 8 was performed. Clinical follow-up of 100 patients with benign diseases of the prostate and with PIN was available. RESULTS: Needle biopsy samples with repeated benign diagnosis resemble BPH specimens taken by TURP in TP53 mutation frequency (TURP: 16.1%, needle biopsy: 21.2%) and later affliction by PCa (TURP: 3/32 = 9.4%, needle biopsy: 8/51 = 15.7%, p = 0.409). Patients with TP53 mutations in needle biopsy samples showed a significantly reduced disease-free survival time for affliction by PCa (log rank: p = 0.0149). This significance is raised by computing exon 6 mutations only with respect to affection by PCa (p = 0.0002). In TURP patients, exon 7-mutations were also significant (p = 0.0086). Needle biopsy TP53 mutations (p = 0.029) had significant predictive values for later affliction by PCa in multivariate analysis. PSA level and patient age had no predictive value for PCa. CONCLUSION: TP53 mutations reduce the PCa-free survival time in patients with needle biopsy of the prostate and primary benign diagnosis. Exon 6 mutations enhance the risk of being affected by PCa 32-fold.
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Genes p53 , Mutación , Hiperplasia Prostática/genética , Neoplasia Intraepitelial Prostática/genética , Neoplasias de la Próstata/genética , Secuencia de Bases , Biopsia con Aguja , Exones , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Masculino , Datos de Secuencia Molecular , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Hiperplasia Prostática/cirugía , Neoplasia Intraepitelial Prostática/metabolismo , Neoplasia Intraepitelial Prostática/patología , Neoplasia Intraepitelial Prostática/cirugía , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugíaRESUMEN
PURPOSE: Tissue polypeptide antigen (TPA) is present in the proteolytic fragments of cytokeratins 8, 18 and 19 as a component of the cytoskeleton of nonsquamous epithelia. HER-2/neu protein is a transmembrane tyrosine kinase cell surface growth factor receptor that is expressed on normal epithelial and some cancer cells. The urokinase-type plasminogen activator receptor (uPAR) is a GPI-linked single-chain glycoprotein. Mutations of the tumour suppressor gene P53 (TP53) are frequently correlated with tumour development and progression. We compared TPA, HER-2/neu and uPAR, and TP53 mutation in tumour-free and bladder cancer patients. MATERIALS AND METHODS: Clinical samples were used from 60 patients with tumours of the urinary bladder and from 9 patients with benign urological diseases. TPA was analyzed by the immunoluminometric assay LIA-mat TPA-MProlifigen. HER-2/neu was measured using the Bayer Oncoprotein test. uPAR was measured with the IMUBIND Total uPAR ELISA Kit. Mutation status in TP53 exons 5, 6, 7 and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included ROC, Mann-Whitney U-test and Pearson's correlation. RESULTS: Pathological concentrations of TPA, HER-2/neu and uPAR are detectable in the serum and in urine of bladder cancer patients. The calculated diagnostic sensitivity for TPA in serum was 68.37%, for TPA in urine 33.3%, for HER-2/neu 86.7% and for uPAR 79.5%. Pathological levels of TPA in serum (p=0.001) and HER-2/neu (p =0.001) were significantly higher in patients with bladder cancer in comparison to the control group. For superficial bladder cancer, the mutation frequency in TP53 was 50%, while for invasive bladder cancer the mutation frequency in TP53 was 100%. Elevated TPA, HER-2/neu and uPAR levels were associated with all grades and stages of bladder cancer. CONCLUSION: TPA, HER-2/neu or uPAR can differ between bladder cancer patients and the control group, but not between superficial and invasive bladder cancer. TP53 mutation frequently occurs in higher stages of bladder tumours.
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Biomarcadores de Tumor/metabolismo , Genes p53/genética , Mutación , Receptor ErbB-2/biosíntesis , Receptores de Superficie Celular/biosíntesis , Antígeno Polipéptido de Tejido/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Membrana Celular/metabolismo , Análisis Mutacional de ADN , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Exones , Femenino , Glicoproteínas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Receptores del Activador de Plasminógeno Tipo UroquinasaRESUMEN
BACKGROUND: Tissue polypeptide antigen (TPA) is a circulating complex of polypeptide fragments from cytokeratins 8, 18 and 19. It is a tumour-related protein. TPA is an indicator of higher cell proliferation. One function of TP53 is the suppression of apoptosis. TP53 mutations are frequently correlated with tumour development in bladder cancer. One function of TP53 is the suppression of apoptosis. We compared TPA expression and TP53 mutation analysis in tumour-free and bladder cancer patients. MATERIALS AND METHODS: We examined 93 patients with bladder cancer, 24 patients with benign urological diseases and a control group of 18 healthy individuals. TPA concentration was measured by immunoluminometric assay with LIA-mat TPA-M Prolifigen. The normal cut-off value was defined at 47 U/I for serum and at 60 U/mmol for creatinine. Screening for TP53 mutations in tissue and urine sediment, amplification of the TP53 gene by polymerase chain reaction (PCR) for the exons 5, 6, 7 and 8 and temperature gradient gel electrophoresis (TGGE) were used to analyse the mutations. Statistical analysis included ROC, Mann-Whitney U-Test and Pearson's correlation. RESULTS: For superficial bladder cancer the mutation frequency in TP53 was 44.8%. We found elevated TPA levels in 45.5% in serum and 36.1% in urine. For invasive bladder cancer the mutation frequency in TP53 was 79.2%. Elevated TPA levels were found in 57.7% in serum and in 58.3% in urine. TPA has a sensitivity of 48.9% in serum and 40.4% in urine; the specificity of TPA is 83% in serum and 100% in urine in comparison with healthy individuals. We found no correlation between TPA level and the inflammation status of the patient. CONCLUSION: This study demonstrated that TP53 mutation frequently occurs in higher stages of bladder tumours. There was no TPA level difference between superficial and invasive bladder cancer. TPA is significantly higher in serum (p = 0.012) and in urine (p = 0.002) in patients with bladder cancer in comparison with control group. TPA in serum is significantly higher in patients with mutation of TP53 (p = 0.046) but not in urine (p = 0.173) in comparison with patients with wild-type TP53.