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Heterogeneity of PD-L1 expression in lung mixed adenocarcinomas and adenosquamous carcinomas

American Journal of Surgical Pathology Feb 17, 2020

Zito Marino F, Rossi G, Montella M, et al. - As lung adenocarcinomas (ADCs) exhibit a high rate of intratumor morphologic heterogeneity that may indicate a heterogenous molecular and immunophenotypic profile, researchers here examined a series of mixed adenocarcinomas (mADCs) and adenosquamous lung carcinomas (AdSqLCs) for the expression of programmed death-ligand 1 (PD-L1) in different intratumor subtypes and/or growth patterns. They picked as many as 73 mADCs and 6 AdSqLCs. They performed comprehensive histologic subtyping, and assessed PD-L1 expression by immunohistochemistry assay using different primary antibodies and automated immunostainers. Overall, 37 of 79 cases (39.2%) (31 mADCs and all AdSqLCs) expressed PD-L1. Twenty-two of 37 PD-L1-positive cases (23.2% mADC and 83% AdSqLC) had heterogenous PD-L1 expression. ADC with solid pattern more frequently showed PD-L1 expression. The heterogeneity of PD-L1 expression was significantly related to the presence of micropapillary and solid patterns. All PD-L1-positive cases were epidermal growth factor receptor wild-type, 2 cases showed PD-L1 expression and ALK rearrangement concomitantly. These data indicate that mADCs and AdSqLCs exhibit quite heterogenous PD-L1 expression, partly explaining the discrepant results between biopsy and surgical resections and discordant clinical effectiveness in regard to PD-L1-positive or negative ADC diagnosed on cytology/small biopsy.
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