PD-L1 is remarkably over-expressed in EBV-associated pulmonary lymphoepithelioma-like carcinoma and related to poor disease-free survival

Abstract

BackgroudProgrammed cell death-ligand 1 (PD-L1) and driver mutations are commonly seen in non-small-cell lung cancer (NSCLC). However, the prevelance of PD-L1 over-expression and its prognostic value in Epstein–Barr virus (EBV) associated pulmonary lymphoepithelioma-like carcinoma (LELC) remains poorly understood.MethodsA total of 214 NSCLC patients and 113 surgically treated pulmonary LELC patients were included. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Correlations between PD-L1 expression and clinicopathological features as well as survival outcomes were analyzed.ResultsThe frequency of PD-L1 over-expression in NSCLC was 51.4%. No significant association was observed between common driver mutations and PD-L1 over-expression. Remakably, the positive rate of PD-L1 in pulmonary LELC was 74.3%. High PD-L1 expression was associated with impaired diseas-free survival (DFS) compared with low PD-L1 expression (p = 0.008). Multivariate analysis shows that PD-L1 expression level, N stage and M stage were independent prognostic factors for DFS. N stage and M stage but not PD-L1 expression level were significantly associated with overall survival (OS).ConclusionsPD-L1 over-expression was not related to common driver mutations in NSCLC. Pulmonary LELC have remarkably high incidence of PD-L1 expression. PD-L1 was a negative prognostic factor for DFS in surgically resected pulmonary LELC. These findings may provide a rationale for immunotarget therapy in this virus-associated lung cancer.

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma

“…In a report by Jiang et al, the PD-L1 (+) in TCs group was associated with longer DFS, which was consistent with our result (P=0.037) (5). In contrast, no prognostic value of this biomarker for LELC of lung was found in Chang and colleagues' retrospective analysis, and Fang et al had observed that high PD-L1 expression in TCs (H score ≥30) was correlated with poor DFS in resectable LELC of lung (4,6). Although there is no agreement on the prognostic significance of PD-L1, these published reports had confirmed that patients with primary pulmonary LELC are a special community with a higher incidence of PD-L1 (+) in TCs and that they might be candidates for immune therapy with PD-L1/PD-1 monoclonal antibodies.…”

“…In limited literature reports, patients with primary pulmonary LELC survive longer than patients with other lung cancer subtypes (1)(2)(3). However, almost thirty-one percent of early stage patients experienced recurrence within five years after multimodality treatment, and nearly thirty-two percent of all patients with lung LELC presented with advanced disease at initial visits (1,(3)(4)(5). Thus, discovery of new therapeutic targets is needed to improve survival and quality of life further for recurrent or metastatic patients.…”

PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC)

“…Using immunohistochemistry (IHC) assays, several Chinese teams have reported prevalences of tumor cell PD-L1 cytoplasmic and/or membrane staining ranging from 39.9% to 65.9% on Chinese NSCLC patient samples [26–31]. In our study, only PD-L1 membrane staining was used to define PD-L1 positivity, generating a positive staining prevalence of 43.1%, which is largely consistent with the 39.9% reported by Yang's group [29].…”

Metastatic lymphoepithelioma-like carcinoma of the lung treated with nivolumab: a case report and focused review of literature

“…More research is needed to determine the optimal assay and cutoff for determining PD-L1 positivity. Three retrospective series analyzed PD-L1 expression in a total of 258 cases of LELC of the lung (11)(12)(13). The threshold for a positive result was membranous expression in >5% tumor cells.…”