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Intratumoral heterogeneity in programmed death‐ligand 1 immunoreactivity is associated with variation in non‐small cell lung carcinoma histotype
Author(s) -
Naso Julia R,
Wang Gang,
Pender Alexandra,
Wong Selina K,
Zhu Jingyao,
Ho Cheryl,
Ionescu Dia,
Zhou Chen
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13983
Subject(s) - adenocarcinoma , carcinoma , medicine , pathology , lung cancer , lung , adenocarcinoma of the lung , oncology , cancer
Aims Accurate assessment of programmed death‐ligand 1 (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 there to be 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 with 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 samples were grouped by predominant histotype, and when histotype areas within a tumour were compared ( P < 0.02). Lepidic areas had significantly lower PD‐L1 levels than other histotype areas within the same tumour ( P < 0.02). Discordance between intratumoral histotype areas at a clinically relevant threshold (PD‐L1 tumour proportion score of 1% or 50%) 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 tumour, whereas over‐representation of lepidic areas may decrease the PD‐L1 score. Evaluation of how histotype representation impacts on the predictive value of PD‐L1 testing is warranted.