RESUMEN
Transitional cell bladder tumors (TCT) is prone to recurrence (60-80%) after tumor resection. Up to 25% of these patients will progress, so it is important to find reliable predictive markers. We analyzed for loss of heterozygosity (LOH) with respect to 13 microsatellites located on 10 different chromosomal arms. This analysis was performed on the urine sediment and tumor tissue from 59 patients with bladder TCT and on the urine and normal-looking mucosa from 25 patients with a history of bladder TCT but no evidence of disease at the time of the study inclusion. The median follow-up period was 23.1 months (range, 2-48 months) for the 59 patients with bladder TCT and 25 months (range, 4-57 months) for the 25 patients without evidence of ongoing active disease. Correlation between LOH and eventual recurrence, progression, and mortality was investigated. In patients with noninvasive TCT, correlation between 11p tumor tissue LOH and recurrence was found. Similarly, 8p LOH in both urine sediment and tumor tissue correlated with progression. Finally, in the group of patients with a history of bladder TCT, normal tissue 8p and/or 11p LOH correlated with recurrence.
Asunto(s)
Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/genética , Pérdida de Heterocigocidad , Repeticiones de Microsatélite , Recurrencia Local de Neoplasia/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/química , Carcinoma de Células Transicionales/orina , ADN de Neoplasias/orina , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/orinaRESUMEN
BACKGROUND: To investigate whether the recently reported evidence of differences in the overall loss of heterozygosity (LOH) frequency between urine and tumour tissue in patients with transitional cell tumours (TCT) of the urinary bladder involved specific chromosomal sites, and their impact in diagnosis. MATERIALS AND METHODS: Blood, tissue and urine specimens were obtained from 55 patients and 25 controls. Sixteen microsatellites were PCR-amplified and blindly analyzed for LOH through a laser-based capillary electrophoresis system. RESULTS: Significant frequence differences between tumour tissue and urine sediment LOH were found in 9q and 11p in non-invasive disease and 14q in invasive disease. There was no significant difference for all the other chromosomal arms analyzed. CONCLUSION: The contribution in the urine sediment of cells belonging to tumours of the same histological classification differs according to the specific genetic alterations these cells carry. Furthermore, the location regarding these differences could indicate regions involved in tumour exfoliation or apoptosis.
Asunto(s)
Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/orina , Pérdida de Heterocigocidad , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/orina , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/patología , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 9/genética , Femenino , Humanos , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: To determine the diagnostic value of plasma DNA microsatellite analysis in patients with transitional cell carcinoma (TCC) of the urinary bladder, by redefining plasma LOH from the equivalent analysis in controls. The method was further tested for MSI (microsatellite instability) and compared with tissue DNA analysis. MATERIALS AND METHODS: Sixteen microsatellites were amplified in leukocyte, plasma and tissue DNA from 40 patients and 28 controls, and analysed in a laser-based, capillary electrophoresis system. Plasma LOH was determined from the controls' cut-off values. RESULTS: The difference between plasma LOH frequency in patients (25% (10/40)) and controls (14% (4/28)) was not significant. Nevertheless, it occurred significantly more often in low rather than high-grade tumors (p=0.03) and controls (p=0.04). Plasma MSI was dependent upon the number of PCR cycles. Tissue LOH was present in 78% (31/40) of the patients and in none of the controls. Tissue MSI was uncommon. CONCLUSION: The results of plasma DNA microsatellite analysis in TCC need cautious interpretation.
Asunto(s)
Carcinoma de Células Transicionales/genética , ADN de Neoplasias/genética , Repeticiones de Microsatélite/genética , Neoplasias de la Vejiga Urinaria/genética , Carcinoma de Células Transicionales/sangre , Carcinoma de Células Transicionales/diagnóstico , Estudios de Casos y Controles , ADN de Neoplasias/sangre , Amplificación de Genes , Humanos , Pérdida de Heterocigocidad , Masculino , Hiperplasia Prostática/sangre , Hiperplasia Prostática/genética , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/diagnósticoRESUMEN
The aim was to evaluate microsatellite analysis of urine sediment (MAUS) as an alternative method to urine cytology for routine diagnosis of patients with transitional cell tumors (TCT) of the urinary bladder. Urine cytology has the advantage of being non-invasive, fast and cheap, but is of limited value because of its low sensitivity. MAUS has previously been found to be a successful alternative method. However, the experimental set-up of such investigations implied exclusion of samples with unfavorable characteristics and use of a large number of markers. In the present study, MAUS was tested on all samples routinely available and a small panel of markers was selected. The urine sediments of 66 TCT patients and 24 controls were analyzed by MAUS with 16 fluorescent markers and by urine cytology. All samples were analyzed, including the ones of later micturition, with gross hematuria, leukocyturia or absence of visible sediment. In patients with tumors of low grade (grades I-II), MAUS was significantly more sensitive than urine cytology. The two methods were of equivalent diagnostic power in high-grade (grades III-IV), high-stage (pT1-pT4) tumors. A panel of the six most informative markers for MAUS was selected. Although MAUS has an advantage over routine cytology in low-grade, low-stage tumors, an overall sensitivity of 45% is not sufficient for routine clinical use.