Metastases of lung adenocarcinoma were found to have varying levels of programmed death-ligand 1 (PD-L1) expression based on histologic pattern, with the highest level present in solid pattern metastases, according to the results of a study published in Lung Cancer.

“The relationship between PD-L1 expression and histopathological subtypes has been shown on primary tumors and not on metastases,” the authors wrote. The aim of this study was to characterize the heterogeneity in PD-L1 expression among different histologic patterns of metastases of lung adenocarcinoma.

The study retrospectively analyzed tumor and metastatic tissue from 136 consecutive patients with metastatic lung adenocarcinoma. Histologic patterns were solid, acinar, papillary, and micropapillary.  The tumor proportional score was used to evaluate PD-L1 expression.

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The most common histologic pattern was solid at 50.7%, followed by acinar at 27.2%, micropapillary at 10.3%, and papillary at 7.3%. There were 42.6% of patients with 2 histologic patterns, 16.2% with 3 patterns, and 2.2% with 4 patterns.

Expression of PD-L1 was highest in the solid pattern with a mean of 28%, followed by micropapillary at 23.6%, 5.3% for acinar, and 5% for papillary.

Among patients with more than 1 histologic pattern, PD-L1 expression was significantly different between the patterns (P ≤.015).

Heterogeneity in PD-L1 expression was also found between metastatic and primary tumor samples, with 24% of patients having tumor proportional scores less than 1% and at least 1% between their samples.

The authors concluded that “These results might explain discrepancies of PD-L1 results between biopsies and surgical samples and the fact that some patients might respond to checkpoint inhibition even though PD-L1 expression is low or absent.”


Forest F, Casteillo F, Da Cruz V, et al. Heterogeneity of PD-L1 expression in lung adenocarcinoma metastasis is related to histopathological subtypes. Lung Cancer. 2021;155:1-9. doi:10.1016/j.lungcan.2021.02.032