Association of PD-L1 Expression With Survival in Large Cell Neuroendocrine Lung Carcinoma and Literature Review

Objective To ascertain the expression of programmed death ligand-1 （PD-L1） on large cell neuroendocrine lung carcinoma （LCNEC）, analysis its association with survival and review existing literatures. Methods Between January 2016 to July 2021, 42 LCNEC patients diagnosed at Department of pathology, Guangdong Provincial People's Hospital with PD-L1 detection were included. PD-L1 expression was analyzed by immunohistochemistry and the association of PD-L1 expression with clinicopathological characteristics and survival were performed. Previously published studies using PubMed search engine were reviewed. Results Forty-two cases of LCNECs were retrieved. Median age was 63 years with male preponderance （85.7%）. Nearly half of patients （42.9%） were smoker. 81% of the specimens were from surgical resection. 47.6% were diagnosed with pure LCNECs and the others were combined LCNECs with small cell lung cancer, adenocarcinoma and squamous carcinoma. Immunostaining of PD-L1 was performed using clone 22C3 with the percentage positivity of 43.2% or SP142 with the percentage positivity of 60% and the overall percentage positivity was 45.2%. Patients with PD-L1 positive showed significantly longer disease-free survival （DFS） but not overall survival （OS） than those with PD-L1 negative, but in Cox regression analysis, PD-L1 was not associated with either DFS or OS. Eleven studies evaluating 713 LCNECs were reviewed. The percentage positivity varied from 10.4%~100%, which was higher in immune cells than that in tumor cells. Moreover, PD-L1 positivity in immune cells was associated with better prognosis, while the association of PD-L1 positivity in tumor cells with prognosis was still inconsistent. Conclusions PD-L1 positivity could be found in part of LCNECs, and DFS in patients with PD-L1 positive tends to be longer.