P2.01-052 High PD-L1 Expression is Associated with Worse Prognosis in Primary Resected Squamous Cell Carcinomas of the Lung

Abstract

Expression of programmed death ligand 1 (PD-L1) is rendered a possible biomarker for immunotherapy targeting programmed death protein 1 (PD1) and PD-L1. Durable clinical responses have been demonstrated in patients with squamous cell carcinoma (SqCC) of the lung. Tumor infiltrating lymphocytes (TILs) are also regarded important players in immunomodulating therapies. Still, there is much uncertainty regarding the expression of the markers and associated tumor characteristics. We aimed to assess the prognostic impact and heterogeneity of PD-L1 expression across two antibodies, in conjunction with TILs, in SqCC of the lung. PD-L1 expression was investigated on a tissue microarray (TMA) of pulmonary SqCC using immunohistochemistry and two different clones (SP142, E1L3N). The cohort comprised all consecutive patients with primary resected pulmonary SqCC, without previous SqCC of other sites, diagnosed 2000-2013 at the Institute of Pathology, University of Bern. Epithelial expression of PD-L1 in primary tumors (n=372) and mediastinal lymph node (LN) metastases (n=27) was evaluated across 8 TMA cores per tumor using the following increment intervals: 0%; 1%; 5%; 10%; 20%; 30%, 50%. Intratumoral and intraepithelial infitrates of CD8+ T lymphocytes were determined. Results were compared with clinic-pathologic parameters including tumor related survival. The staining results correlated significantly between the two antibodies (r=0.822; p<0.001) with the best congruence for tumors with ≤1% or ≥30% positivity. These tumors had also very homogenous staining results across all TMA cores, indicating low levels of intratumoral heterogeneity, in contrast to tumors with 1-30% PD-L1 positivity (p<0.001 both antibodies). Stainings correlated significantly between primary tumors and LN metastases (p<0.001 both antibodies). High PD-L1 expression correlated with intratumoral and intraepithelial CD8+ lymphocyte counts in primaries (p<0.001 both antibodies). PD-L1 expression was not significantly associated with pT or pN staging. High PD-L1 expression was associated with shorter tumor related survival. Cut-offs with the best prognostic discrimination were 30% positivity for SP142 and 50% for E1LN3 in univariate analysis (p=0.001/p=0.008). PD-L1 expression, pT category and age of the patients, but not CD8+ TILs were independent prognostic factors in multivariate analysis (HR=2.265, p=0.013 for SP142; HR=2.323, p=0.014 for E1LN3). PD-L1 expression was an independent predictor of shorter tumor related survival in pulmonary SqCC across all stages. The homogeneity of PD-L1 expression in “no” or “high” staining tumors across different cores and primary versus LN metastases indicates a valid assessment on small tissue samples and LN-metastases.