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.
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.
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.
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.
Urologic oncology. 2021 Feb 06 [Epub ahead of print]
Gang Wang, Peter C Black, Peter J Goebell, Lingyun Ji, Carlos Cordon-Cardo, Bernd Schmitz-Dräger, Debra Hawes, Bogdan Czerniak, Sarah Minner, Guido Sauter, Frederic Waldman, Susan Groshen, Richard J Cote, Colin P Dinney
Department of Pathology, University of British Columbia, Vancouver, Canada., Department of Urologic Sciences, University of British Columbia, Vancouver, Canada. Electronic address: ., Department of Urology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany., Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA., Department of Pathology, Icahn School of Medicine at Mount Sinai, New York City, NY., Department of Urology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany; Urologie 24, Nürnberg, Germany., Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA., Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX., Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Department of Laboratory Medicine and Urology, University of California San Francisco, San Francisco, CA., Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX.