PD-L1 expression in bronchopulmonary neuroendocrine tumors: correlation with morphological features and prognosis

Abstract

The purpose of the study was to estimate the programmed death-ligand 1 (PD-L1) expression in lung NETs (Grade 2 and Grade 3) and it’s possible relation to clinicopathological features and patients outcome. Materials and methods. The study was performed using surgical material and biopsies from 40 patients with lung neuroendocrine tumors (NETs) before chemotherapy prescribing. Morphological study and immunohistochemistry (IHC) were applied. Necrosis, fibrosis, lymphocytic infiltration, neoangiogenesis, Ki-67 and PD-L1 rates, and metastatic lesions and patients’ survival were estimated using nonparametric statistics. Results. PD-L1 didn’t show any significant association with studied morphological indicators and tumors grade. PD-L1 and Ki-67 expression rates were not significantly associated. But there was a significant difference in median survival rates at different levels of PD-L1 expression. In group 0 (PD-L1 negative tumors) the median survival was 85.37 months; in group 1 (PD-L1 rates 1–5%) it decreased sharply to 8 months, and in group 2 (PD-L1 expression 6–20%) it critically decreased again and did not exceed 1 month. The probability that a patient in group 1 will die earlier than a patient in group 0 was 71%. The same risks were observed while comparing the events in group 2 and group 1. The probability that a patient in group 2 will die earlier than a patient in group 0 was 86%. Conclusions. PD-L1 expression is considered a prospective target for immunotherapy, but it also may be closely related to prognosis. In the current study 72.5% lung NETs expressed PD-L1. Moderately differentiated atypical carcinoids showed substantial aggressiveness, 69.23% of them were PD-L1 positive. There was no significant association of PD-L1 rates with tumors Grade, proliferative index (Ki67) and morphological features (necrosis, fibrosis, lymphocytic infiltration and angiogenesis). But patients’ life expectancy was closely connected to the level of PD-L1 expression in lung NETs Grade 3. The higher the expression rate of PD-L1, the shorter the patients’ life expectancy. In PD-L1 negative cases median survival was 85 months; at low PD-L1 expression (1–5%) it dropped sharply to 8 months, and at moderate PD-L1 expression (6–20%) it decreased even more — to 0,8 months. The probability of an earlier death increased significantly (71%) even at low PD-L1 expression (1–5%) and exceeded 80% at PD-L1 rate 6–20%. PD-L1 should be considered as additional negative prognostic factor in lung NETs Grade 3.