The Search for the Optimal cut-off Value of p53-Immunohistochemistry to Predict Prognosis of Invasive Bladder Cancer : A Multi-Center, Multi-Laboratory Analysis
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
International journal of surgical pathology - 31(2023), 2 vom: 01. Apr., Seite 157-166 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mertens, Laura S [VerfasserIn] |
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| Links: |
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| Themen: |
Bladder cancer |
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| Anmerkungen: |
Date Completed 15.03.2023 Date Revised 15.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/10668969221095173 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339958391 |
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| 100 | 1 | |a Mertens, Laura S |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Search for the Optimal cut-off Value of p53-Immunohistochemistry to Predict Prognosis of Invasive Bladder Cancer |b A Multi-Center, Multi-Laboratory Analysis |
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| 500 | |a Date Completed 15.03.2023 | ||
| 500 | |a Date Revised 15.03.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a bladder cancer | |
| 650 | 4 | |a immunohistochemistry | |
| 650 | 4 | |a p53 | |
| 650 | 4 | |a prognosis | |
| 650 | 4 | |a radical cystectomy | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 700 | 1 | |a Claps, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Mayr, Roman |e verfasserin |4 aut | |
| 700 | 1 | |a Hodgson, Anjelica |e verfasserin |4 aut | |
| 700 | 1 | |a Shariat, Shahrokh F |e verfasserin |4 aut | |
| 700 | 1 | |a Hippe, Katrin |e verfasserin |4 aut | |
| 700 | 1 | |a Neuzillet, Yann |e verfasserin |4 aut | |
| 700 | 1 | |a Sanders, Joyce |e verfasserin |4 aut | |
| 700 | 1 | |a Burger, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a Pouessel, Damien |e verfasserin |4 aut | |
| 700 | 1 | |a Otto, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a van der Kwast, Theo H |e verfasserin |4 aut | |
| 700 | 1 | |a Lotan, Yair |e verfasserin |4 aut | |
| 700 | 1 | |a Allory, Yves |e verfasserin |4 aut | |
| 700 | 1 | |a Downes, Michelle R |e verfasserin |4 aut | |
| 700 | 1 | |a van Rhijn, Bas W G |e verfasserin |4 aut | |
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