Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom; Royal Marsden Hospital, Sutton, United Kingdom.
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom.
EBioMedicine. 2023 Feb;88:104436. doi: 10.1016/j.ebiom.2023.104436. Epub 2023 Jan 26.
Protein markers of cellular proliferation, hypoxia, apoptosis, cell cycle checkpoints, growth factor signalling and inflammation in localised prostate tumours have previously shown prognostic ability. A translational substudy within the CHHiP trial of radiotherapy fractionation evaluated whether these could improve prediction of prognosis and assist treatment stratification following either conventional or hypofractionated radiotherapy.
Using case:control methodology, patients with biochemical or clinical failure after radiotherapy (BCR) were matched to patients without recurrence according to established prognostic factors (Gleason score, presenting PSA, tumour-stage) and fractionation schedule. Immunohistochemical (IHC) staining of diagnostic biopsy sections was performed and scored for HIF1α, Bcl-2, Ki67, Geminin, p16, p53, p-chk1 and PTEN. Univariable and multivariable conditional logistic regression models, adjusted for matching strata and age, estimated the prognostic value of each IHC biomarker, including interaction terms to determine BCR prediction according to fractionation.
IHC results were available for up to 336 tumours. PTEN, Geminin, mean Ki67 and max Ki67 were prognostic after adjusting for multiple comparisons and were fitted in a multivariable model (n = 212, 106 matched pairs). Here, PTEN and Geminin showed significant prediction of prognosis. No marker predicted BCR according to fractionation.
Geminin or Ki67, and PTEN, predicted response to radiotherapy independently of established prognostic factors. These results provide essential independent external validation of previous findings and confirm a role for these markers in treatment stratification.
Cancer Research UK (BIDD) grant (A12518), Cancer Research UK (C8262/A7253), Department of Health, Prostate Cancer UK, Movember Foundation, NIHR Biomedical Research Centre at Royal Marsden/ICR.
局部前列腺肿瘤中的细胞增殖、缺氧、细胞凋亡、细胞周期检查点、生长因子信号和炎症的蛋白标志物先前已显示出预后能力。放疗分割 CHHiP 试验中的一项转化子研究评估了这些标志物是否可以改善预后预测，并在常规或低分割放疗后协助治疗分层。
使用病例对照方法，根据既定的预后因素（Gleason 评分、首发 PSA、肿瘤分期）和分割方案，将放疗后生化或临床失败（BCR）的患者与无复发的患者相匹配。对诊断性活检切片进行免疫组织化学（IHC）染色，并对 HIF1α、Bcl-2、Ki67、Geminin、p16、p53、p-chk1 和 PTEN 进行评分。单变量和多变量条件逻辑回归模型，根据匹配层和年龄进行调整，估计每个 IHC 生物标志物的预后价值，包括交互项，以根据分割确定 BCR 预测。
多达 336 个肿瘤的 IHC 结果可用。PTEN、Geminin、平均 Ki67 和最大 Ki67 在进行多次比较调整后具有预后意义，并纳入多变量模型（n=212，106 对匹配）。在这里，PTEN 和 Geminin 显示出对预后的显著预测作用。没有标志物根据分割预测 BCR。
Geminin 或 Ki67 和 PTEN 独立于既定的预后因素预测对放疗的反应。这些结果为之前的发现提供了重要的独立外部验证，并证实了这些标志物在治疗分层中的作用。
英国癌症研究协会（BIDD）拨款（A12518）、英国癌症研究协会（C8262/A7253）、卫生部、英国前列腺癌协会、莫特基金会、皇家马斯登/ICR 国家健康研究所生物医学研究中心。
