Julia R Naso1, Gang Wang2, Alexandra Pender3, Selina K Wong3, Jingyao Zhu4, Cheryl Ho3, Diana N Ionescu2, Chen Zhou2. 1. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. 2. Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada. 3. Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada. 4. Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Abstract
AIMS: Accurate assessment of PD-L1 levels in non-small cell lung carcinoma (NSCLC) samples is complicated by intratumoral heterogeneity. We aimed to (i) establish whether intratumoral PD-L1 variation is associated with differences in local histotype, (ii) identify histotypes associated with a tendency for higher or lower PD-L1 scores, and (iii) estimate the frequency of clinically significant discordance in PD-L1 levels between intratumoral histotype areas. METHODS AND RESULTS: We reviewed 166 NSCLC resection specimens clinically tested for PD-L1 using the 22C3 pharmDx assay. Multiple histotypes were present in 55% (68/123) of non-mucinous adenocarcinoma samples. Solid histotypes had significantly higher PD-L1 levels than other histotypes, both when grouping samples by predominant histotype and when histotype areas within a tumor were compared (p-values <0.02). Lepidic areas had significantly lower PD-L1 levels than other histotypes areas within the same tumor (p-values <0.02). Discordance between intratumoral histotype areas at a clinically relevant threshold (1% or 50% PD-L1 tumor proportion score) was present in 32% (22/68) of non-mucinous adenocarcinoma specimens with multiple histotype areas. The lepidic histotype was most frequently involved in discordance. CONCLUSIONS: Intratumoral heterogeneity in PD-L1 is associated with variation in histotype. Over-representation of solid areas may increase the PD-L1 score assigned to a tumor, whereas over-representing lepidic areas may decrease the PD-L1 score. Evaluation of how histotype representation impacts the predictive value of PD-L1 testing is warranted. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
AIMS: Accurate assessment of PD-L1 levels in non-small cell lung carcinoma (NSCLC) samples is complicated by intratumoral heterogeneity. We aimed to (i) establish whether intratumoral PD-L1 variation is associated with differences in local histotype, (ii) identify histotypes associated with a tendency for higher or lower PD-L1 scores, and (iii) estimate the frequency of clinically significant discordance in PD-L1 levels between intratumoral histotype areas. METHODS AND RESULTS: We reviewed 166 NSCLC resection specimens clinically tested for PD-L1 using the 22C3 pharmDx assay. Multiple histotypes were present in 55% (68/123) of non-mucinous adenocarcinoma samples. Solid histotypes had significantly higher PD-L1 levels than other histotypes, both when grouping samples by predominant histotype and when histotype areas within a tumor were compared (p-values <0.02). Lepidic areas had significantly lower PD-L1 levels than other histotypes areas within the same tumor (p-values <0.02). Discordance between intratumoral histotype areas at a clinically relevant threshold (1% or 50% PD-L1tumor proportion score) was present in 32% (22/68) of non-mucinous adenocarcinoma specimens with multiple histotype areas. The lepidic histotype was most frequently involved in discordance. CONCLUSIONS: Intratumoral heterogeneity in PD-L1 is associated with variation in histotype. Over-representation of solid areas may increase the PD-L1 score assigned to a tumor, whereas over-representing lepidic areas may decrease the PD-L1 score. Evaluation of how histotype representation impacts the predictive value of PD-L1 testing is warranted. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Authors: Steven Bozinovski; Amanda Vannitamby; Kanishka Rangamuwa; Savreet Aujla; Hao Wang; Christian Aloe; Louis Irving; Tracy T Leong; Daniel P Steinfort Journal: Transl Lung Cancer Res Date: 2021-06