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Multi-candidate immunohistochemical markers to assess radiation response and prognosis in prostate cancer: results from the CHHiP trial of radiotherapy fractionationResearch in context

التفاصيل البيبلوغرافية
العنوان: Multi-candidate immunohistochemical markers to assess radiation response and prognosis in prostate cancer: results from the CHHiP trial of radiotherapy fractionationResearch in context
المؤلفون: Anna Wilkins, Barry Gusterson, Holly Tovey, Clare Griffin, Christine Stuttle, Frances Daley, Catherine M. Corbishley, David Dearnaley, Emma Hall, Navita Somaiah
المصدر: EBioMedicine, Vol 88, Iss , Pp 104436- (2023)
بيانات النشر: Elsevier, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Fractionation, Immunohistochemistry, Prostate cancer, Radiotherapy, Treatment stratification, Medicine, Medicine (General), R5-920
الوصف: Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396423000014; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2023.104436
URL الوصول: https://doaj.org/article/a5b636b3bc8543eaa61edfe616f51293
رقم الأكسشن: edsdoj.5b636b3bc8543eaa61edfe616f51293
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2023.104436