The 16th World Conference on Lung Cancer (WCLC) was held on 6-9 September 2015 in Denver, Colorado. Organized by the International Association for the Study of Lung Cancer (IASLC) and a local organizing committee, the WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies.
Dr Bernadette Reyna Asuncion, Research Fellow from A/Prof Richie Soong’s group, submitted an abstract for the conference. She was subsequently selected as a recipient of the Developing Nations Award for her continued interest and current research in lung cancer.
Congratulations to Dr Asuncion on her award!
Dr. Asuncion with Dr. Fred R. Hirsch, WCLC 2015 Congress President and IASLC Chief Executive Officer.
PD-L1 Expression in Tumor Infiltrating Immune Cells Determined by Digital Imaging Is Associated with Poor Survival in NSCLC Patients
Bernadette Reyna Asuncion1, Zul Fazreen1, Mohd Feroz Mohd Omar2, Nur Lina Mohd Salleh2, Michelle Ann Rozario2, Min-En Nga2, Yin Huei Pang2, Brendan Pang2, Marie Loh3, Byoung Chul Cho4, Barry Iacopetta5, Richie Soong1,2, Ross A. Soo1,6,7
1 Cancer Science Institute of Singapore, Singapore,
2 Department of Pathology, NUHS, Singapore,
3 Agency for Science Tech and Research, Singapore,
4 Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea,
5 University of Western Australia, Perth, ACT/Australia,
6 Department of Haematology-Oncology, National University Cancer institute, NUHS, Singapore,
7 School of Surgery, University of Western Australia
Programmed Death-Ligand 1 (PD-L1) has emerged as a potential prognostic marker and as an effective target for therapeutic inhibition in cancer. Using digital slide imaging, we evaluated the clinical, molecular and survival associations of PD-L1 expression in non-small cell lung cancer (NSCLC) according to cell type and tissue localization. The automated, objective assessment of cell shape, localization and number provided by this technology, with staining intensity, promises to be a useful aid to pathologists when reviewing staining patterns at high resolution.
The objective of this study was to assess PD-L1 expression in tumor and immune cells in NSCLC at high resolution by digital slide imaging. PD-L1 expression was then correlated with clinicopathological and molecular features of NSCLC, as well as with overall survival.
Tissue arrays containing 1.6mm diameter core samples of tumor from 199 patients with resected NSCLC were constructed and stained for PD-L1 by immunohistochemistry (IHC) and quantitatively assessed using the Vectra slide imaging system for PD-L1 tumor membrane expression (TME), PD-L1 positive (+) tumor immune cell density (TICD) and PD-L1+ stroma immune cell density (SICD). A PD-L1 tumor membrane H-score was calculated by adding the products of proportions and intensity at each intensity levels of 0-3 to a maximum score of 300. Assessment of gene mutation and anaplastic lymphoma kinase rearrangement were performed using the AmpliSeq Cancer Hotspot V2 assay and IHC, respectively.
Density plot analysis revealed bimodal distributions for PD-L1 TME, TICD and SICD. High PD-L1 TME correlated with larger tumor size, squamous cell histology and poor differentiation. PD-L1+ TICD was associated with male gender and wild-type EGFR. Univariate analysis revealed that stage (p=0.001), PD-L1 TME (p=0.007) and PD-L1+ TICD (p=0.006) were associated with worse survival. Iterative p-value analysis indicated the optimal thresholds for PD-L1 TME were 30 (p=0.003, 73% of cases) or 160 (p<0.001, 7%), while for PD-L1+ TICD they were 6.9% (p=0.022, 33%) or 20% (p=0.001, 5%). In multivariate analysis, stage (p=0.018), PD-L1 TME≥160 (p=0.040) and PD-L1+ TICD≥6.9% (p=0.015) were independently associated with survival.
PD-L1 TME and PD-L1+ TICD expression determined by digital analysis have prognostic value in NSCLC.