PD-L1 expression pattern in large cell neuroendocrine carcinoma of the lung

Background: Large cell neuroendocrine carcinomas of the lung (LCNECs) are rare neoplasms with limited therapeutics options. Pathological diagnostic of LCNECs is morphologically based, may be difficult and need immunohistochemical (IHC) analysis. Immune checkpoint inhibitors targeting tumoral and immune cells interaction have changed the NSCLC treatment but few data are available on LCNECs immune environment and particularly the expression of PD-L1 on both tumors (TC) and immune infiltrating (IC) cells. The objective of the present study is to determine the expression and pattern of PD-L1 staining in a cohort of LCNECs patients. Methods: Clinical files and tumors biopsies of patients (pts) with a LCNEC diagnosed between 01.01.2014 and 31.12.2016 were retrospectively collected (GFPC 03-2017). All histological samples were centrally reviewed by six pathologists, according to the latest WHO 2015 classification. LCNEC was confirmed and PD-L1 expression was determined both in TC and IC, using the anti-PD-L1 antibody 22C3 (kit and automat Dako). PD-L1 expression was scored on TC as the percentage of PD-L1 positive cells (0 to 100%). PD-L1 expression on IC was determined as follows: IC0: positive IC representing < 1% of the tumor surface; IC1 : positive IC representing ≥1% but <5 % of the tumor surface ; IC2 : positive IC representing ≥ 5% but <10% of the tumor surface ; and IC3 : positive IC representing >10% of the tumor surface. Results: 86pts were initially included in the study, 28 (32%) were excluded for non-LCNEC diagnosis. Among the 58 pts with LCNEC, five (8%) had a composite LCNEC with a NSCLC component. The mean age of the population was 65 years, mainly mens (86%) and former or current heavy smokers (93%). PD-L1 was positive on TC for only 12% of the samples, while 76 % of the samples shows IC PD-L1 positive, with respectively 18 (35%) IC3, 8(14%) IC2, and 13(25%) IC1. Conclusions: LCNEC display a particular PDL1 expression pattern, different from NSCLC and from SCLC and may suggest a potential effectiveness of therapeutic anti PD-L1 antibodies, this hypothesis have to be addressed in clinical trial. Legal entity responsible for the study: GFPC. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.