RESUMO
Deletions of chromosome arm 13q belong to the most frequent molecular alterations in prostate cancer. To better understand the role of 13q deletion in prostate cancer we took advantage of our large prostate cancer tissue microarray comprising more than 12 000 cancer samples with full pathological and clinical follow-up data. Fluorescence in situ hybridization with probes for ENOX1 (13q14.11) and the retinoblastoma gene (RB1, 13q14.2) was employed. A 13q deletion was found in 21% of 7375 analyzable cancers. Deletions were always heterozygous and associated with high Gleason grade (P < .0001), advanced tumor stage (P < .0001), high preoperative prostate-specific antigen (PSA) levels (P = .0125), lymph node metastasis (P = .0377), positive resection margin (P = .0064), and early biochemical recurrence (P < .0001). 13q deletions were marginally more frequent in prostate cancers with negative ERG status (22.9%) than in ERG-positive tumors (18.7%; P < .0001). Loss of 13q predicted patient prognosis independently from established prognostic parameters that are available at the time of biopsy (P = .0004), including preoperative PSA level, clinical tumor stage, and biopsy Gleason grade. In summary, the results of our study identify 13q deletion as a frequent event in prostate cancer, which is linked to an adverse phenotype and poor prognosis in this disease.
Assuntos
Biomarcadores Tumorais/genética , Deleção Cromossômica , Cromossomos Humanos Par 13/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Deleção de Genes , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , NADH NADPH Oxirredutases/genética , Gradação de Tumores , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Proteína do Retinoblastoma/genética , Análise Serial de TecidosRESUMO
Development of genetic instability is a hallmark of tumor progression. Type III ß-tubulin (TUBB3) is a component of microtubules involved in chromosome segregation. Its overexpression has been linked to adverse features of urinary bladder cancer. To investigate the role of TUBB3 for development of genetic instability, we compared TUBB3 expression with histopathological features and surrogate markers of genetic instability and tumor aggressiveness; copy number changes of HER2, TOP2A, CCND1, RAF1, and FGFR1; nuclear accumulation of p53, and cell proliferation in a tissue microarray (TMA) with more than 700 bladder cancers. TUBB3 expression was linked to high-grade and advanced-stage cancers (P<.0001), rapid cell proliferation (P<.0001), presence of multiple gene copy number alterations (P=.0008), and nuclear accumulation of p53 (P=.0008). Strong TUBB3 staining was found in 43% of urothelial cancers harboring copy number alterations as compared with 28% of genetically stable cancers, and in 50% of p53-positive cancers as compared with 30% of p53-negative tumors. The fraction of tumors with concomitant TUBB3 and p53 positivity increased with tumor stage and grade: 2% in pTaG1-2, 11% in pTaG3, 17% in pT1G2, 23% in pT1G3, and 32% in pT2-4 cancers (P<.0001). Importantly, strong TUBB3 overexpression was detectable in about 20% of low-grade, noninvasive cancers. In summary, our study demonstrates that TUBB3 overexpression is linked to an aggressive subtype of urinary bladder cancers, which is characterized by increased genetic instability, p53 alterations, and rapid cell proliferation. Detection of TUBB3 overexpression in genetically stable, low-grade, and noninvasive bladder cancers may be clinically useful to identify patients requiring particular close monitoring.
Assuntos
Biomarcadores Tumorais/análise , Instabilidade Genômica , Tubulina (Proteína)/análise , Neoplasias da Bexiga Urinária/química , Biomarcadores Tumorais/genética , Biópsia , Proliferação de Células , Variações do Número de Cópias de DNA , Dosagem de Genes , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Gradação de Tumores , Estadiamento de Neoplasias , Fenótipo , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/genética , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Patients with atrial fibrillation (AF) are at high risk of stroke. More than 15% of all strokes are due to atrial fibrillation. So far anticoagulation is the treatment of choice with a risk reduction of almost 70%. On the other hand, anticoagulation has many side effects such as intracranial or gastrointestinal hemorrhage. Closing the left atrial appendage (LAA) might be an alternative in patients who cannot take anticoagulation treatment due to contraindications or conditions in which the hazard of hemorrhage is greater than the potential clinical benefit. The PLAATO system (Percutaneous Left Atrial Appendage Transcatheter Occlusion) is a new device to close the LAA by the catheter technique. The device consists of a self-expandable nitinol cage that is covered with ePTFE. It is delivered via a specially designed 12F transseptal sheath. Small anchors along the struts prevent the occluder from embolizing. After device implantation patients are placed on aspirin only. The results of the dog model and the first clinical experiences in humans have been very promising.