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The Search for the Optimal cut-off Value of p53-Immunohistochemistry to Predict Prognosis of Invasive Bladder Cancer: A Multi-Center, Multi-Laboratory Analysis
LS. Mertens, F. Claps, R. Mayr, A. Hodgson, SF. Shariat, K. Hippe, Y. Neuzillet, J. Sanders, M. Burger, D. Pouessel, W. Otto, TH. van der Kwast, Y. Lotan, Y. Allory, MR. Downes, BWG. van Rhijn
Language English Country United States
Document type Multicenter Study, Journal Article
- MeSH
- Cystectomy MeSH
- Genes, p53 MeSH
- Immunohistochemistry MeSH
- Humans MeSH
- Tumor Suppressor Protein p53 * genetics MeSH
- Urinary Bladder Neoplasms * diagnosis surgery genetics MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Introduction: Mutations in the TP53 gene are indicative of worse outcome in bladder cancer and are usually assessed by immunohistochemistry. To define p53-overexpression, a threshold of >10% is most commonly used (cut-off1). Recently, a novel cut-off (aberrant = 0% or ≥50%) (cut-off2) showed better correlation to clinical outcome. In this study, we evaluate the association between p53-immunohistochemistry cut-offs, clinico-pathological variables and disease-specific survival (DSS). Methods: Seven-hundred-fifty chemotherapy-naïve patients who underwent radical cystectomy were included (92% muscle-invasive bladder cancer. In addition to cut-off1 and cut-off2, a third cut-off (cut-off3) was determined based on the highest Youden-index value. Cut-off values were associated with clinico-pathological variables and FGFR3 mutation status. The Kaplan-Meier method was used to estimate DSS. Results: Aberrant p53-expression was found in 489 (65%) (cut-off1) and 466 (62%) (cut-off2) tumors. Cut-off3 was determined at 25% and aberrant p53-expression in 410 cases (55%) (cutoff3). p53-expression levels were significantly associated with higher pT-stage (cut-off1/2/3: P = 0.047, P = 0.006 and P = 0.0002, respectively), higher grade (all, P < 0.0001), and FGFR3 wild-type (cut-off1: P = 0.02, cut-offs2&3: P = 0.001). Median follow-up was 5.3 years (interquartile range, 4.0-6.0 years). p53-expression was not associated with DSS for any of the three cut-offs (cut-off1/2/3: P-log-rank = 0.566, 0.77 and 0.50, respectively). If we only considered locally advanced bladder cancer, results on DSS remained non-significant. Conclusion: This multi-center, multi-laboratory study showed that, regardless of the cut-off used, p53-immunohistochemistry did not enable selection of patients with worse outcome. Our results suggest that p53-immunohistochemistry alone is not suitable to guide clinical decision making after radical cystectomy.
Department of Laboratory Medicine and Pathobiology 7938University of Toronto Toronto ON Canada
Department of Pathology Institute Curie Paris France
Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Department of Urology Hôpital Foch UVSQ Paris Saclay University Suresnes France
Department of Urology University of Texas Southwestern Medical center Dallas TX USA
Department of Urology Weill Cornell Medical College New York NY USA
Dept Pathology University Medical Center Regensburg Regensburg Germany
Institut Curie CNRS UMR144 Molecular Oncology team PSL Research University Paris France
References provided by Crossref.org
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