Prominent Nucleoli and Non-glandular Feature Are Independent Predictors of PD-L1 Expression in Lung Adenocarcinoma

Background/Aim: In patients with non-small cell lung cancer, relationships between PD-L1 (programmed death-ligand 1) expression and clinicopathological characteristics have been examined. However, the association between cytological features and PD-L1 expression remains unknown. Thus, the aim of this study was to investigate whether nuclear features might be correlated with PD-L1 expression in patients with advanced and inoperable lung adenocarcinoma using small biopsy specimens. Materials and Methods: Archived slides from 90 patients with lung adenocarcinoma who underwent small biopsy between October 2014 and May 2017 at the Incheon St. Mary's Hospital, were reviewed. PD-L1 expression was detected by immunohistochemistry using PD-L1 22C3 IHC assay. Associations of PD-L1 expression with pathological and molecular features (EGFR mutation, ALK and ROS-1 rearrangement) were statistically analyzed. Results: PD-L1 expression in tumor cells was positive in 33 of 90 cases (36.7%). Higher PD-L1 expression (≥50%) was more frequent in cases with marked nuclear pleomorphism (p<0.001), coarse chromatin pattern (p=0.006), predominant nucleoli (≥3 μm) (p<0.001), large nuclear diameter (>5x small lymphocyte) (p=0.006), non-glandular feature (p<0.001), and atypical mitosis (p=0.034). There were no significant correlations between PD-L1 positivity and molecular features. In multivariable logistic regression analysis, PD-L1 positivity was independently associated with prominent nucleoli (p=0.005) and non-glandular feature (p=0.007). Conclusion: Prominent nucleoli and non-glandular feature are independent predictors of PD-L1 expression in lung adenocarcinoma.

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