Institute of Pathology, Indian Council of Medical Research, Post Box no. 4909, Safdarjung Hospital Campus, New Delhi 110029, India.
Pathol Oncol Res. 2011 Mar;17(1):91-101. doi: 10.1007/s12253-010-9287-1. Epub 2010 Jun 23.
Non muscle invasive bladder cancers recur frequently and identification of biomarkers for predicting recurrence are necessary. The present study evaluated the individual and synergistic effects of tumor suppressor (p53/p21waf1) and angiogenesis [vascular endothelial growth factor (VEGF)/endoglin (CD105)] markers. The study included 90 cases of non muscle invasive bladder cancer. Cell spots were stained with primary antibodies and Flourescein isothiocyanate (FITC). Slides were observed under confocal laser scanning microscope for protein expression. The association between the markers individually and synergistically with recurrence were assessed by a χ2 and Fisher's Exact test. Survival analysis was performed to predict recurrence and test for significant difference in recurrence free survival probability. Recurrence [overall:39(43.3%) and low grade(LG):26(54.2%)] was significant with p53 and VEGF expression and the profiles p53/VEGF, p53/CD105, VEGF/CD105, p53/p21/CD105, p53/VEGF/CD105 and all four were significantly associated with recurrence in both groups. In the multivariable model the [HR(95%CI),p: overall and LG] profiles p21/VEGF [2.195(1.052-4.582),0.036; 3.425(1.332-8.811),0.011], VEGF/CD105[2.624(1.274-5.403),0.009 and 3.380(1.348-8.472),0.009], p53/p21/CD105 [2.000(0.993-4.027),0.052 and 2.539(1.047-6.157),0.039], p53/VEGF/CD105 [2.360(1.148-4.849),0.020 and 2.738(1.104-6.788),0.030], p21/VEGF/CD105 [2.611(1.189-5.731),0.017 and 3.946(1.530-10.182),0.005] and all four [2.382(1.021-5.556),0.045 and 3.572(1.287-9.911),0.014] significantly predicted the recurrence along with significant log rank. In the pTa subset (n = 33) the profiles p53/p21, p53/CD105, p21/VEGF, VEGF/CD105, p53/VEGF/CD105, p53/p21/CD105 and p21/VEGF/CD105, significantly predicted hazard for recurrence. The present study emphasizes an underlying association between tumor suppressor (p21waf1) and angiogenesis (VEGF/CD105) biomarkers. In addition combination profiles appeared to indicate an aggressive nature with high propensity for recurrence in LG and pTa tumours.
非肌肉浸润性膀胱癌经常复发，因此需要寻找预测复发的生物标志物。本研究评估了肿瘤抑制因子（p53/p21waf1）和血管生成（血管内皮生长因子[VEGF]/内皮糖蛋白[CD105]）标志物的单独和协同作用。本研究包括 90 例非肌肉浸润性膀胱癌患者。使用针对细胞斑点的一抗和异硫氰酸荧光素（FITC）进行染色。在共聚焦激光扫描显微镜下观察载玻片，以检测蛋白表达。通过卡方检验和 Fisher 确切概率法评估标志物单独和协同与复发的相关性。进行生存分析以预测复发，并测试无复发生存率的显著差异。复发[总体：39（43.3%）和低级别（LG）：26（54.2%）]与 p53 和 VEGF 表达显著相关，且 p53/VEGF、p53/CD105、VEGF/CD105、p53/p21/CD105、p53/VEGF/CD105 和所有四个标志物在两个组中均与复发显著相关。在多变量模型中，[HR（95%CI），p：总体和 LG]p21/VEGF 谱[2.195（1.052-4.582），0.036；3.425（1.332-8.811），0.011]、VEGF/CD105 谱[2.624（1.274-5.403），0.009 和 3.380（1.348-8.472），0.009]、p53/p21/CD105 谱[2.000（0.993-4.027），0.052 和 2.539（1.047-6.157），0.039]、p53/VEGF/CD105 谱[2.360（1.148-4.849），0.020 和 2.738（1.104-6.788），0.030]、p21/VEGF/CD105 谱[2.611（1.189-5.731），0.017 和 3.946（1.530-10.182），0.005]和所有四个标志物[2.382（1.021-5.556），0.045 和 3.572（1.287-9.911），0.014]显著预测了复发，且对数秩检验具有显著意义。在 pTa 亚组（n=33）中，p53/p21、p53/CD105、p21/VEGF、VEGF/CD105、p53/VEGF/CD105、p53/p21/CD105 和 p21/VEGF/CD105 谱显著预测了 LG 和 pTa 肿瘤的复发风险。本研究强调了肿瘤抑制因子（p21waf1）和血管生成（VEGF/CD105）标志物之间的潜在关联。此外，组合谱似乎表明具有高度复发倾向的侵袭性特征。
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