Supplementary Table S4 from Analytic, Preanalytic, and Clinical Validation of p53 IHC for Detection of TP53 Missense Mutation in Prostate Cancer
journal contribution
posted on 2023-03-31, 19:30 authored by Liana B. Guedes, Fawaz Almutairi, Michael C. Haffner, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Kasra Yousefi, Rajni Sharma, Angelo M. De Marzo, George J. Netto, William B. Isaacs, Ashley E. Ross, Edward M. Schaeffer, Tamara L. LotanDemographic and clinical-pathologic characteristics of eligible patients in intermediate/high risk radical prostatectomy cohort
Funding
CDMRP
NIH
NCI
History
ARTICLE ABSTRACT
Purpose: TP53 missense mutations may help to identify prostate cancer with lethal potential. Here, we preanalytically, analytically, and clinically validated a robust IHC assay to detect subclonal and focal TP53 missense mutations in prostate cancer.Experimental Design: The p53 IHC assay was performed in a CLIA-accredited laboratory on the Ventana Benchmark immunostaining system. p53 protein nuclear accumulation was defined as any p53 nuclear labeling in >10% of tumor cells. Fifty-four formalin-fixed paraffin embedded (FFPE) cell lines from the NCI-60 panel and 103 FFPE prostate cancer tissues (88 primary adenocarcinomas, 15 metastases) with known TP53 mutation status were studied. DU145 and VCaP xenografts were subjected to varying fixation conditions to investigate the effects of preanalytic variables. Clinical validation was performed in two partially overlapping radical prostatectomy cohorts.Results: p53 nuclear accumulation by IHC was 100% sensitive for detection of TP53 missense mutations in the NCI-60 panel (25/25 missense mutations correctly identified). Lack of p53 nuclear accumulation was 86% (25/29) specific for absence of TP53 missense mutation. In FFPE prostate tumors, the positive predictive value of p53 nuclear accumulation for underlying missense mutation was 84% (38/45), whereas the negative predictive value was 97% (56/58). In a cohort of men who experienced biochemical recurrence after RP, the multivariable HR for metastasis among cases with p53 nuclear accumulation compared with those without was 2.55 (95% confidence interval, 1.1–5.91).Conclusions: IHC is widely available method to assess for the presence of deleterious and heterogeneous TP53 missense mutations in clinical prostate cancer specimens. Clin Cancer Res; 23(16); 4693–703. ©2017 AACR.Usage metrics
Licence
Exports
RefWorksRefWorks
BibTeXBibTeX
Ref. managerRef. manager
EndnoteEndnote
DataCiteDataCite
NLMNLM
DCDC