Ekta Jain1, Shivani Sharma2, Aditi Aggarwal3, Nitin Bhardwaj4, Aditi Dewan5, Abhishek Kumar6, Deepika Jain7, Munmun Bhattacharya8, Gauraw Kumar Saurav9, Lata Kini10, Sambit Kumar Mohanty11. 1. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: ektajain86@gmail.com. 2. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: shivani.sharma@corediagnostics.in. 3. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: aditi.aggarwal@corediagnostics.in. 4. Indian Council of Medical Research and National Institute of Malaria Research, New Delhi, 110029, India. Electronic address: nitinbh529@gmail.com. 5. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: aditi.dewan@corediagnostics.in. 6. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: abhishek.kumar@corediagnostics.in. 7. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: deepika.jain@corediagnostics.in. 8. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: munmun.bhattacharya@corediagnostics.in. 9. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: gauraw.kumar@corediagnostics.in. 10. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: lata.kini@gmail.com. 11. Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India. Electronic address: sambit.mohanty@corediagnostics.in.
Abstract
BACKGROUND: Immunotherapy with checkpoint inhibitor programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies targeting the cellular immune checkpoints is the present area of interest showing promising results in patients with advanced non-small cell lung cancer (NSCLC). As there is paucity of PD-L1 expression data from the Indian perspective, we studied the correlation of clinicopathologic profile and oncogenic driver mutations in these patients. MATERIALS AND METHODS: Samples from 252 advanced NSCLCs patients were studied for PD-L1 expression through immunohistochemistry using rabbit anti-human PD-L1 monoclonal antibody (clone SP263) on Ventana BenchMark ULTRA autostainer. Simultaneously, genetic mutations were studied by next generation sequencing (for EGFR, ALK, ROS, MET, and BRAF). PD-L1 expression was analyzed for association with clinicopathologic features and various mutations. RESULTS: PD-L1 positivity was seen in 134 patients (53.2 %). It was twice more prevalent in males than females. No significant correlation was observed between PD-L1 expression with age, gender, site of testing (primary vs. metastatic tumors), smoking status, tumor laterality, stage, or histologic type; however, there was significant difference among solid and acinar types of adenocarcinoma combined together vs. other adenocarcinoma subtypes (p = 0.013), and well and moderately differentiated vs. poorly differentiated tumors (p = 0.022). When types/extent of PD-L1 positivity (≥25 %) were compared with demographics, clinical, and pathologic variables, significant differences were observed across the tumor grades (high-grade vs. low-grade) (p = 0.009) and stages (p = 0.039). The PD-L1 expression failed to demonstrate any statistical significance with oncogenic drivers. High PD-L1 expression (TPS ≥ 50) was observed in 27.6 % patients, and it was more prevalent in female patients (32.4 %), aged ≥60 years (33.8 %), smokers (27.3 %), poorly differentiated (36.8 %) and stage IV tumors (28.2 %). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors. CONCLUSIONS: This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.
BACKGROUND: Immunotherapy with checkpoint inhibitor programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies targeting the cellular immune checkpoints is the present area of interest showing promising results in patients with advanced non-small cell lung cancer (NSCLC). As there is paucity of PD-L1 expression data from the Indian perspective, we studied the correlation of clinicopathologic profile and oncogenic driver mutations in these patients. MATERIALS AND METHODS: Samples from 252 advanced NSCLCs patients were studied for PD-L1 expression through immunohistochemistry using rabbit anti-human PD-L1 monoclonal antibody (clone SP263) on Ventana BenchMark ULTRA autostainer. Simultaneously, genetic mutations were studied by next generation sequencing (for EGFR, ALK, ROS, MET, and BRAF). PD-L1 expression was analyzed for association with clinicopathologic features and various mutations. RESULTS: PD-L1 positivity was seen in 134 patients (53.2 %). It was twice more prevalent in males than females. No significant correlation was observed between PD-L1 expression with age, gender, site of testing (primary vs. metastatic tumors), smoking status, tumor laterality, stage, or histologic type; however, there was significant difference among solid and acinar types of adenocarcinoma combined together vs. other adenocarcinoma subtypes (p = 0.013), and well and moderately differentiated vs. poorly differentiated tumors (p = 0.022). When types/extent of PD-L1 positivity (≥25 %) were compared with demographics, clinical, and pathologic variables, significant differences were observed across the tumor grades (high-grade vs. low-grade) (p = 0.009) and stages (p = 0.039). The PD-L1 expression failed to demonstrate any statistical significance with oncogenic drivers. High PD-L1 expression (TPS ≥ 50) was observed in 27.6 % patients, and it was more prevalent in female patients (32.4 %), aged ≥60 years (33.8 %), smokers (27.3 %), poorly differentiated (36.8 %) and stage IV tumors (28.2 %). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors. CONCLUSIONS: This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.