Programmed death ligand-1 expression and its association with the degree of differentiation and the presence of necrosis in non-small cell lung carcinoma

Abstract

The mechanisms underlying the expression of programmed death ligand-1 (PD-L1) in non-small cell lung carcinoma (NSCLC) are not yet fully clarified. In this study, surgical resections of 730 lung cancer patients with diagnosed NSCLC were analyzed. Results of PD-L1 immunohistochemistry (using clone 22C3) were correlated with clinicopathological variables including the degree of tumor differentiation and the presence of confluent areas of coagulative necrosis. PD-L1 immunohistochemistry was analyzed in tumor cells, whereas PD-L1 positivity was defined as membranous staining in ≥ 1 of tumor cells. A significantly higher proportion of PD-L1 positive cases was noted in poorly differentiated (grade 3) adenocarcinomas compared to better differentiated (grade 1 and grade 2) subtypes (63.8 % vs. 28.7 %; p < 0.001). Contrary to this, better differentiated (keratinizing) and less differentiated (non-keratinizing) squamous cell carcinoma subtypes were found to have a similar proportion of PD-L1 positive cases (51.4 % vs. 55.8 %; p = 0.570). High levels of PD-L1 expression significantly correlated with the presence of necrosis in NSCLC: seventy-nine of 109 NSCLC cases with the presence of necrosis were PD-L1 positive compared to 256 out of 621 NSCLC without necrosis (72.5 % vs. 41.2 %; p < 0.001). High PD-L1 expression was not positively correlated with age, gender, and advanced T stage but a significant association between PD-L1 positivity and higher N stage was observed (p < 0.001) in NSCLC patients. In conclusion, the proportion of PD-L1 positive cases is higher only in poorly differentiated NSCLC of the adenocarcinoma type. A significantly higher overall rate of PD-L1 positive cases was noted in NSCLC with the presence of necrosis. Further investigation is suggested to elucidate the intricated interconnections between the plethora of hypoxic biomarkers and immunological factors in different types and subtypes of NSCLC.

Keywords: Hypoxia-inducible factor 1; Hypoxic signaling pathways; Non-small cell lung carcinoma; Programmed death ligand-1.