Polyamine-modulated factor-1 methylation predicts Bacillus Calmette-Guérin response in patients with high-grade non-muscle-invasive bladder carcinoma
| Autor: | Jesus Fernandez-Gomez, Virginia Cebrian, Marta Sanchez-Carbayo, Florentino Fresno, Safwan Escaf, Miguel Alvarez-Múgica |
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| Rok vydání: | 2012 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Pathology Lymphovascular invasion Urology Disease-Free Survival Epigenesis Genetic Adjuvants Immunologic Internal medicine medicine Carcinoma Humans Cumulative incidence Aged Proportional Hazards Models Retrospective Studies Aged 80 and over Univariate analysis Bladder cancer business.industry Carcinoma in situ Standard treatment Hazard ratio DNA Methylation Middle Aged medicine.disease Administration Intravesical Treatment Outcome Urinary Bladder Neoplasms Spain BCG Vaccine Disease Progression Female Neoplasm Recurrence Local business Follow-Up Studies Transcription Factors |
| Zdroj: | European urology. 63(2) |
| ISSN: | 1873-7560 |
| Popis: | Background Bacillus Calmette-Guerin (BCG) is a standard treatment to reduce tumor recurrence and delay progression of high-risk non–muscle-invasive (NMI) bladder tumors. However, it is not clear yet which patients are more likely to respond to BCG. Objective The aim was to evaluate the role of polyamine-modulated factor-1 (PMF-1) methylation in predicting clinical outcome of T1 high-grade (T1HG) bladder tumors treated with BCG. Design, setting, and participants In a retrospective design, PMF-1 methylation was analyzed on tumor specimens belonging to 108 patients with T1HG NMI bladder cancer undergoing BCG treatment. Median follow-up was 77 mo (range: 5–235 mo). Outcome measurements and statistical analysis PMF-1 methylation was assessed by methylation-specific polymerase chain reactions. Recurrence, progression into muscle-invasive tumors, and disease-specific survival rates were analyzed using competing risks regression analysis. Results and limitations Among the 108 patients analyzed, 35 had recurring disease (32.4%), 21 progressed (19.4%), and 16 died of disease (14.8%); 71.3% of tumors had PMF-1 methylation. Univariate analyses using cumulative incidence curves revealed that an unmethylated PMF-1 was significantly associated with increased recurrence ( p = 0.026), progression ( p = 0.01), and shorter disease-specific survival (log-rank, p = 0.03). Multivariate analyses indicated that among sex, age, focality, tumor size, and concomitant carcinoma in situ, only PMF-1 methylation provided significant hazard ratios (HRs) for recurrence of (HR: 2.032; p = 0.042), and progression (HR: 2.910; p = 0.020). Limitations of the study include its retrospective design, lymphovascular invasion status not available, short maintenance BCG, and that a second transurethral resection was not performed. Conclusions Epigenetic analyses revealed that the methylation status of PMF-1 was associated with the clinical outcome of patients with T1HG tumors undergoing BCG treatment. An unmethylated PMF-1 correlated to recurrence and progression in T1HG disease using univariate and multivariate analyses. Thus, assessing the methylation status of PMF-1 may serve to distinguish patients responding to BCG from those who may require more aggressive therapeutic approaches. |
| Databáze: | OpenAIRE |
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