Mertens, Laura S. and Claps, Francesco and Mayr, Roman and Hodgson, Anjelica and Shariat, Shahrokh F. and Hippe, Katrin and Neuzillet, Yann and Sanders, Joyce and Burger, Maximilian and Pouessel, Damien and Otto, Wolfgang and van der Kwast, Theo H. and Lotan, Yair and Allory, Yves and Downes, Michelle R. and van Rhijn, Bas W. G. (2023) The Search for the Optimal cut-off Value of p53-Immunohistochemistry to Predict Prognosis of Invasive Bladder Cancer: A Multi-Center, Multi-Laboratory Analysis. INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY, 31 (2): 1066896922. pp. 157-166. ISSN 1066-8969, 1940-2465
Full text not available from this repository. (Request a copy)Abstract
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-naive 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | P53 IMMUNOHISTOCHEMISTRY; MUTATIONS; GRADE; GENE; bladder cancer; radical cystectomy; p53; immunohistochemistry; prognosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Mar 2024 11:06 |
| Last Modified: | 05 Mar 2024 11:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58355 |
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