@article{3639e70c445148d5bee5cc3b094f2f1a,
title = "Prognostic markers in pT3 bladder cancer: A study from the international bladder cancer tissue microarray project",
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",
author = "Gang Wang and Black, {Peter C.} and Goebell, {Peter J.} and Lingyun Ji and Carlos Cordon-Cardo and Bernd Schmitz-Dr{\"a}ger and Debra Hawes and Bogdan Czerniak and Sarah Minner and Guido Sauter and Frederic Waldman and Susan Groshen and Cote, {Richard J.} and Dinney, {Colin P.}",
note = "Funding Information: This project was supported by NIH/NCI Cancer Center Core Grant P30CA16672 and the GU Bladder Cancer SPORE CA91846 (NCI). Support was also received by the NCI Bladder Marker Network U01CA070903, and the NCI p53/MVAC Trial R01CA071921. We gratefully acknowledge the investigators at all the sites who contributed tissue to this project:, Steven Shen, Baylor College of Medicine, Houston, USA. Peter Clark, Wake Forest University, USA. Badar Mian, Albany Medical College, USA. Charles Rosser, University of Florida Shands ? Jacksonville, USA. Walter Stadler, University of Chicago, USA. Colin Dinney & Bogdan Czerniak, The University of Texas, MD Anderson Cancer Center, USA. Susan Groshen & Richard Cote, University of Southern California, USA. Frederic Waldman, University of California, San Francisco, USA. Carlos Cordon-Cardo, Memorial Sloan Kettering Cancer Center, USA. Dan Theodorescu, University of Virginia, USA. Robert Getzenberg, University of Pittsburgh, USA. Yves Fradet, Laval University, Canada. Martin Gleave, University of British Columbia, Canada. Jack Schalken, University Hospital Nijmegen, the Netherlands. Margaret Knowles, St. James?s Univ. Hospital, England. Tapani Liukkonen, University of Tampere, Finland. Christer Busch, University Hospital, Uppsala, Sweden. Guido Sauter, Basel University Hospital, Switzerland and University of Hamburg, Germany. Feliksas Jankevicius, Vilnius University, Lithuania. Helmut Klocker and Thomas Akkad, Medical University Innsbruck, Austria. Arndt Hartmann, University of Regensburg, Germany. Peter Goebell, University of Essen, Germany. Funding Information: This project was supported by NIH/NCI Cancer Center Core Grant P30CA16672 and the GU Bladder Cancer SPORE CA91846 (NCI). Support was also received by the NCI Bladder Marker Network U01CA070903, and the NCI p53/MVAC Trial R01CA071921. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = may,
doi = "10.1016/j.urolonc.2021.01.021",
language = "English (US)",
volume = "39",
pages = "301.e17--301.e28",
journal = "Urologic Oncology: Seminars and Original Investigations",
issn = "1078-1439",
publisher = "Elsevier Inc.",
number = "5",
}