Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study
Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study
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DOI：
10.1016/s1470-2045(08)70076-7
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发表时间：
2008-04-01
期刊：
影响因子：
51.1
通讯作者：
Parker, Chris
中科院分区：
文献类型：
--
作者：
Vergis, Roy;Corbishley, Catherine M.;Parker, Chris
背景：肿瘤缺氧和血管生成的内在标志物的表达是几种癌症放射治疗和可能的手术预后的重要预测因素。局限性前列腺癌的肿瘤缺氧程度与其他癌症相当，但关于肿瘤缺氧程度与治疗结果的关系的数据很少。我们的目的是研究肿瘤缺氧和血管生成的内在标志物在局部前列腺癌中的预测价值，包括放疗和手术治疗的患者。方法：我们应用一种新的针活检组织微阵列（TMA）技术来研究两项随机对照放疗剂量递增试验中治疗的局部、未治疗的前列腺癌患者的诊断样本。采用Cox比例风险法进行多因素分析，以评估临床结果、生化控制与缺氧诱导因子-1 α (HIF-1 α)、血管内皮生长因子（VEGF）和骨桥蛋白表达的免疫组化染色之间的关系。该分析在一个独立的系列中重复进行，这些男性患有局部的，以前未经治疗的前列腺癌，并接受根治性前列腺切除术。主要指标为生化时间（即前列腺特异性抗原[PSA]）失败。在1995年10月12日至2002年2月5日期间，308名患者在伦敦皇家马斯登医院和英国萨顿进行了两项前瞻性随机试验，其中201名患者进行了放射治疗队列和诊断活检。1995年6月6日至2005年11月4日期间，329名患者从丹麦斯基比的奥胡斯大学医院被确定为前列腺切除术队列；其中，40例患者因肿瘤太小而无法取样（19例），因为石蜡块太薄（19例），或者因为石蜡块缺失（2例）而被排除在外，留下289例患者进行分析。对于接受放疗的患者，多因素分析显示，VEGF （p=0.008）和HIF-1 α (p=0.02)表达升高，而骨钙蛋白表达不升高（p=0.978），与临床肿瘤分期、Gleason评分、血清PSA浓度和放疗剂量无关，是生化失败时间较短的显著预测因素。对于接受手术治疗的患者，VEGF染色升高(p
Background Expression of intrinsic markers of tumour hypoxia and angiogenesis are important predictors of radiotherapeutic, and possibly surgical, outcome in several cancers. Extent of tumour hypoxia in localised prostate cancer is comparable to that in other cancers, but few data exist on the association of extent of tumour hypoxia with treatment outcome. We aimed to study the predictive value of intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer, both in patients treated with radiotherapy and in those treated surgically.Methods We applied a new, needle biopsy tissue microarray (TMA) technique to study diagnostic samples from men with localised, previously untreated prostate cancer treated in two randomised controlled trials of radiotherapy-dose escalation. Multivariate analysis by Cox proportional hazards was done to assess the association between clinical outcome, in terms of biochemical control, and immunohistochemical staining of hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and osteopontin expression. The analysis was repeated on an independent series of men with localised, previously untreated prostate cancer treated by radical prostatectomy. The main outcome was time to biochemical (ie, prostate-specific antigen [PSA]) failure.Findings Between Oct 12, 1995, and Feb 5, 2002, 308 patients were identified from two prospective, randomised trials at the Royal Marsden Hospital, London and Sutton, UK, for the radiotherapy cohort and diagnostic biopsies were available for 201 of these patients. Between June 6, 1995, and Nov 4, 2005, 329 patients were identified from the Aarhus University Hospital, Skejby, Denmark, for the prostatectomy cohort; of these, 40 patients were excluded because the tumour was too small to sample (19 patients), because the paraffin block was too thin (19 patients), or because the blocks were missing (two patients), leaving 289 patients for analysis. For patients treated with radiotherapy, increased staining for VEGF (p=0.008) and HIF-1 alpha (p=0.02) expression, but not increased osteopontin expression (p=0.978), were significant predictors of a shorter time to biochemical failure on multivariate analysis, independent of clinical tumour stage, Gleason score, serum PSA concentration, and dose of radiotherapy. For patients treated with surgery, increased staining for VEGF (p