Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 May;39(5):301.e17-301.e28.
doi: 10.1016/j.urolonc.2021.01.021. Epub 2021 Feb 7.

Prognostic markers in pT3 bladder cancer: A study from the international bladder cancer tissue microarray project

Gang Wang  1 , Peter C Black  2 , Peter J Goebell  3 , Lingyun Ji  4 , Carlos Cordon-Cardo  5 , Bernd Schmitz-Dräger  6 , Debra Hawes  7 , Bogdan Czerniak  8 , Sarah Minner  9 , Guido Sauter  9 , Frederic Waldman  10 , Susan Groshen  4 , Richard J Cote  11 , Colin P Dinney  12
Affiliations
Multicenter Study

Prognostic markers in pT3 bladder cancer: A study from the international bladder cancer tissue microarray project

Gang Wang et al. Urol Oncol. 2021 May.

Abstract

Purpose: We evaluated the prognostic value of 10 putative tumor markers by immunohistochemistry in a large multi-institutional cohort of patients with locally advanced urothelial cancer of the bladder (UCB) with the aim to validate their clinical value and to harmonize protocols for their evaluation.

Materials and methods: Primary tumor specimens from 576 patients with pathologic (p)T3 UCB were collected from 24 institutions in North America and Europe. Three replicate 0.6-mm core diameter samples were collected for the construction of a tissue microarray (TMA). Immunohistochemistry (IHC) for 10 previously described tumor markers was performed and scored at 3 laboratories independently according to a standardized protocol. Associations between marker positivity and freedom from recurrence (FFR) or overall survival (OS) were analyzed separately for each individual laboratory using Cox regression analysis.

Results: The overall agreement of the IHC scoring among laboratories was poor. Correlation among the 3 laboratories varied across the 10 markers. There was generally a lack of association between the individual markers and FFR or OS. The number of altered cell cycle regulators (p53, Rb, and p21) was associated with increased risk of cancer recurrence (P < 0.032). There was no clear pattern in the relationship between the percentage of markers altered in an 8-marker panel and FFR or OS.

Conclusions: This large international TMA of locally advanced (pT3) UCB suggests that altered expression of p53, Rb, and p21 is associated with worse outcome. However this study also highlights limitations in the reproducibility of IHC even in the most expert hands.

Keywords: Bladder cancer; Prognostic Markers; Tissue microarray.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:
Hematoxylin & eosin-stained slide of the tissue microarray.
Figure 2:
Figure 2:. Freedom from recurrence (A) and overall survival (B) stratified by pathologic N-Stage.
Kaplan-Meier curve depicting freedom from recurrence (FFR) and overall survival (OS), by N-stage of the disease.
Figure 3:
Figure 3:. Patient outcome according to marker status.
Log of hazard ratios (HR) and 95% confidence intervals for patients scored as marker positive compared to those scored as marker negative. A HR of 0 on the log scale corresponds to a HR of 1, indicating a lack of association. If HR on the log scale is >0 (i.e., HR>1), it indicates that the marker positivity is associated with an unfavorable outcome.
Figure 3:
Figure 3:. Patient outcome according to marker status.
Log of hazard ratios (HR) and 95% confidence intervals for patients scored as marker positive compared to those scored as marker negative. A HR of 0 on the log scale corresponds to a HR of 1, indicating a lack of association. If HR on the log scale is >0 (i.e., HR>1), it indicates that the marker positivity is associated with an unfavorable outcome.
Figure 4:
Figure 4:. Consensus Analyses
-- Log of hazard ratios and 95% confidence intervals for patients scored as marker positive compared to those scored as marker negative.
Figure 5:
Figure 5:. Freedom from recurrence stratified by the number of altered markers in a panel of three cell cycle regulators (Rb, p21 and p53).
Kaplan-Meier curve depicting freedom from recurrence (FFR) by the number of altered markers (Rb, p21 and p53), in Lab A (A), Lab B (B), Lab C (C) and consensus analysis (D).
Figure 5:
Figure 5:. Freedom from recurrence stratified by the number of altered markers in a panel of three cell cycle regulators (Rb, p21 and p53).
Kaplan-Meier curve depicting freedom from recurrence (FFR) by the number of altered markers (Rb, p21 and p53), in Lab A (A), Lab B (B), Lab C (C) and consensus analysis (D).
See this image and copyright information in PMC

Comment in

References

    1. Shariat SF, Karakiewicz PI, Palapattu GS, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: A contemporary series from the bladder cancer research consortium. Journal of Urology. 2006;176(6):2414–2422. - PubMed
    1. Esrig D, Spruck CH 3rd, Nichols PW, et al. p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer. The American journal of pathology. 1993;143(5):1389–1397. - PMC - PubMed
    1. Esrig D, Elmajian D, Groshen S, et al. Accumulation of nuclear p53 and tumor progression in bladder cancer. The New England journal of medicine. 1994;331(19):1259–1264. - PubMed
    1. Cote RJ, Esrig D, Groshen S, Jones PA, Skinner DG. p53 and treatment of bladder cancer. Nature. 1997;385(6612):123–124. - PubMed
    1. Stadler WM, Lerner SP, Groshen S, et al. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011;29(25):3443–3449. - PMC - PubMed

Publication types

Substances