PD-L1 expression in urothelial carcinoma with predominant or pure variant histology: Concordance among 3 commonly used and commercially available antibodies Journal Article


Authors: Reis, H.; Serrette, R.; Posada, J.; Lu, V.; Chen, Y. B.; Gopalan, A.; Fine, S. W.; Tickoo, S. K.; Sirintrapun, S. J.; Iyer, G.; Funt, S. A.; Teo, M. Y.; Rosenberg, J. E.; Bajorin, D. F.; Dalbagni, G.; Bochner, B. H.; Solit, D. B.; Reuter, V. E.; Al-Ahmadie, H. A.
Article Title: PD-L1 expression in urothelial carcinoma with predominant or pure variant histology: Concordance among 3 commonly used and commercially available antibodies
Abstract: The introduction of immune checkpoint blockade (ICB) therapy has transformed the management of advanced bladder cancer (BC). Despite its limitations, PD-L1 immunohistochemistry may serve as a predictive biomarker of anti-PD-L1/PD1 therapy. While urothelial carcinoma (UC) patients with predominant or pure variant histology (UCV) account for up to one-third of advanced cases, to date, most ICB BC studies have excluded patients with such histologies. To assess the potential utility of ICB in patients with UCV, we analyzed PD-L1 expression in UCV and compared 3 commonly used and commercially available PD-L1 antibodies. Full sections from 84 UCV cases were stained with clones SP263, 22C3, and SP142, all of which are considered predictive assays to identify UC patients who are more likely to respond to anti-PD-1/PD-L1 inhibitors durvalumab, pembrolizumab, and atezolizumab, respectively. Expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) was assessed. Staining extent and characteristics were evaluated, and concordance among the 3 clones was determined at various cutoff points as used in previous studies in BC. We found that PD-L1 was expressed in a significant percentage of UCV cases at different cutoff points (cutoff 1% TC: 37% to 54%, cutoff 5% TC: 23% to 37%), with the highest expression in UC with squamous differentiation. These figures are equal to or higher than those for classic/pure UC (4% to 30%). The results suggest that patients with UCV may benefit from anti-PD-1/PD-L1 therapy and argue against the exclusion of UC with predominant or pure variant histology from clinical ICB studies. The highest expression in both TC and IC was observed with clone SP263, followed by 22C3 and SP142, and all clones showed strong agreement in a pairwise comparison, both in TC and IC (R-values: 0.780 to 0.901), which indicates that all 3 clones are potentially useful in the evaluation of PD-L1 expression in UCV. © 2019 Wolters Kluwer Health, Inc.
Keywords: immunohistochemistry; urothelial carcinoma; concordance; pd-l1; immune therapy; variant histology
Journal Title: American Journal of Surgical Pathology
Volume: 43
Issue: 7
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2019-07-01
Start Page: 920
End Page: 927
Language: English
DOI: 10.1097/pas.0000000000001264
PUBMED: 31135485
PROVIDER: scopus
PMCID: PMC6561805
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Dean Bajorin
    438 Bajorin
  2. Guido Dalbagni
    261 Dalbagni
  3. David Solit
    464 Solit
  4. Satish K Tickoo
    375 Tickoo
  5. Anuradha Gopalan
    292 Gopalan
  6. Gopakumar Vasudeva Iyer
    139 Iyer
  7. Yingbei Chen
    242 Chen
  8. Bernard Bochner
    332 Bochner
  9. Samson W Fine
    335 Fine
  10. Victor Reuter
    976 Reuter
  11. Jonathan Eric Rosenberg
    237 Rosenberg
  12. Samuel Aaron Funt
    25 Funt
  13. Min Yuen   Teo
    30 Teo
  14. Henning Reis
    2 Reis
  15. Jennifer Posada
    1 Posada
  16. Vincent Lu
    1 Lu