Open Access

ARTICLE

Standardizing immunohistochemistry methodology for evaluation of PD-1 and PDL-1 expression in upper tract urothelial carcinoma

Luca Campedel^1,†, Thomas Seisen^1,†, Justine Varinot², Géraldine Cancel-Tassin^2,3,#, Alain Ruffion⁴, Emilien Seizilles De Mazancourt⁴, Myriam Decaussin-Petrucci⁵, Grégoire Robert⁶, Nam-Son Vuong⁶, Magali Philipp⁷, Eva Compérat^2,3,#, Morgan Rouprêt^1,3,#, Olivier Cussenot^2,3,#

1 Sorbonne Université, GRC n°5, Predictive Onco-Urology, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France
2 Sorbonne Université, GRC n°5, Predictive Onco-Urology, AP-HP, Hôpital Tenon, Paris, France
3 CeRePP, Hôpital Tenon, Paris, France
4 Urology Department, Hospices Civils de Lyon, Lyon, France
5 Pathology Department, Hospices Civils de Lyon, Lyon, France
6 Urology Department, Centre Hospitalo-Universitaire de Bordeaux, Bordeaux, France
7 Pathology Department, Centre Hospitalo-Universitaire de Bordeaux, Bordeaux, France
† contributed equally to this paper
# IRCI = The International Rare Cancer Initiative Rare GU Working Group

Canadian Journal of Urology 2021, 28(3), 10719-10724.

Abstract

Introduction: Controversy regarding the prognostic and/or predictive role of PD-1 and PD-L1 expression for upper tract urothelial carcinoma (UTUC) could partly be explained by inconsistencies in the immunohistochemistry (IHC) methodology. The objective is to standardize the methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC patients.
Materials and methods: Twenty-two cases treated with radical nephroureterectomy between 1996 and 2015 at 11 French hospitals were randomly selected to compare different methodologies for evaluation of PD-1 and PD-L1 expression. IHC was carried out on whole tissue sections and 0.6 mm- or 2 mm-core tissue micro-arrays (TMAs) using PD-1 NAT105 and PD-L1 28.8 or E1L3N on both tumor cells and tumor-infiltrating immune cells (TILs). Results obtained with whole tissue sections (WTS) were compared to those obtained with 0.6 mm- and 2 mm-core TMAs. Concordance was evaluated using Kappa coefficient.
Results: For evaluation of PD-1 and PD-L1 expression, the best concordance with WTS was observed using the PD-1 NAT105 and PD-L1 28.8 antibody on 2 mm-core TMAs, with a 5% cut-off for positivity on TILs and tumor cells, respectively (Kappa = 0.8).
Conclusions: The most accurate methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC may be based on 2 mm-core TMAs using NAT105 and 28.8 antibodies with a 5% cut-off for positivity on TILs and tumor cells, respectively.

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