Szarvas Tibor
Semmelweis Egyetem, I. sz. Patológiai, és Kísérleti Rákkutató, Intézet, 1085 Budapest, Ulloi út 26.
Magy Onkol. 2009 Dec;53(4):385-9. doi: 10.1556/MOnkol.53.2009.4.8.
Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.
膀胱癌是影响泌尿系统的第二常见恶性肿瘤。目前，组织学是确定治疗方案和患者预后的唯一工具。由于非侵袭性（Ta/T1）和肌肉侵袭性（T2-T4）膀胱肿瘤的治疗方法完全不同，正确分期很重要，尽管它常常受到干扰因素的阻碍。分子方法为早期疾病检测、明确组织学结果的确认及预后评估提供了新的前景。应用分子生物学方法，本研究旨在寻找膀胱癌当前诊断和预后问题的答案。我们分析了334例膀胱癌患者和117例对照个体的肿瘤、血液和/或尿液样本。通过使用12种荧光标记引物的基于PCR的微卫星杂合性缺失（LOH）分析以及使用4种探针的基于DNA杂交的UroVysion FISH技术，对患者和对照的尿液样本进行基因改变分析，以评估这些方法的诊断价值。对膀胱癌患者的肿瘤和血液标本进行全基因组微卫星分析（使用400个标记），以寻找染色体区域，其缺失可能与肿瘤分期相关。此外，我们评估了Tie2、VEGF、血管生成素-1和-2的预后价值。我们得出结论，通过微卫星分析和FISH对排尿尿液样本进行DNA分析是检测膀胱癌的敏感且非侵入性方法。此外，我们建立了一组微卫星标记物，可区分非侵袭性和侵袭性膀胱癌。然而，需要在更大的患者队列中进行进一步分析，以评估它们的特异性和敏感性。最后，我们确定高Ang-2和低Tie2基因表达是肿瘤复发和癌症相关生存的重要且独立的危险因素。
