PD-L1 expression and its clinicopathologic and genomic correlation in the non-small cell lung carcinoma patients: An Indian perspective.

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. 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. 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. 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.

Jain E ，Sharma S ，Aggarwal A ，Bhardwaj N ，Dewan A ，Kumar A ，Jain D ，Bhattacharya M ，Saurav GK ，Kini L ，Mohanty SK ... -  《-》

Comprehensive molecular analysis of driver mutations in non-small cell lung carcinomas and its correlation with PD-L1 expression, An Indian perspective.

Aggarwal A ，Sharma S ，Brar Z ，Kumar V ，Kumar A ，Katara R ，Mohanty SK ... -  《-》

[Correlation Study on Expression of PD-1 and PD-L1 in Non-small Cell Lung Cancer and Epidermal Growth Factor Receptor Mutations].

Jiang L ，Lin Z ，Li N ，Jiang J ，Lu C ，Du S ，Zhang J ，Wang Y ，Chen J ，Gong P ... -  《-》

Common driver mutations and programmed death-ligand 1 expression in advanced non-small cell lung cancer in smokers and never smokers.

In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking. In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked < 20, 20-39, and ≥ 40 pack-years, respectively. The level of PD-L1 expression, assessed using Ventana SP263 monoclonal antibody assay, was defined by the tumor proportion score (TPS) as high expression (TPS ≥ 50%), low expression (TPS 1%-49%) and no expression (TPS < 1%). 101 (52.9%) of 191 advanced NSCLC patients were never smokers. EGFR mutations were more common in never smokers (64.4%) than in smokers (17.8%) with advanced NSCLC (P < 0.0001). A higher proportion of smokers (26.7%) had high PD-L1 expression compared to never smokers (13.9%) (P = 0.042). There was a trend for a higher proportion of male NSCLC patients [28 of 115 (24.3%)] than female patients [10 of 76 (13.2%)] to have high PD-L1 expression (P = 0.087]. High PD-L1 expression was seen in 32 of 110 (29.1%) patients with EGFR wild-type NSCLC but only in 6 of 81 (7.4%) patients with EGFR-mutant tumors (P < 0.0001). Among the 90 smokers with NSCLC, a higher proportion of heavy smokers (35.8%) than non-heavy smokers (13.5%) had high PD-L1 expression (P = 0.034). In patients with adenocarcinoma, high PD-L1 expression was seen in 25 of 77 (32.5%) patients with EGFR wild-type tumors but only in 4 of 70 (5.7%) patients with EGFR-mutant tumors (P < 0.0001). Among patients with adenocarcinoma, a significantly higher proportion of ever smokers (29.3%) than never smokers (13.5%) had high PD-L1 expression (P = 0.032). Among smokers with adenocarcinoma, a significantly higher proportion of heavy smokers (44.1%) than non-heavy smokers (8.3%) had high PD-L1 expression (P = 0.004). On multivariate analysis, after adjusting for gender and smoking status, heavy smoking and EGFR wild-type tumors remained significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma. Heavy smoking and EGFR wild-type tumors were significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma.

Liam CK ，Yew CY ，Pang YK ，Wong CK ，Poh ME ，Tan JL ，Soo CI ，Loh TC ，Chin KK ，Munusamy V ，Liam YS ，Ibrahim NH ... -  《BMC CANCER》

Association of Lung Adenocarcinoma Subtypes According to the IASLC/ATS/ERS Classification and Programmed Cell Death Ligand 1 (PD-L1) Expression in Tumor Cells.

Background: Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features. Patients and Methods: PD-L1 expression was assessed by immunohistochemistry (IHC). According to its positivity in tumor cells membrane, we stratified patients in three different tumor proportions score (TPS) cut-off points: a) <1% (negative), b) between 1 and 49%, and c) ≥50%; afterward, we analyzed the association among PD-L1 expression and lung adenocarcinoma (LADC) predominant subtypes, as well as other clinical features. As an exploratory outcome we evaluated if a PD-L1 TPS score ≥15% was useful as a biomarker for determining survival. Results: A total of 240 patients were included to our final analysis. Median age at diagnosis was 65 years (range 23-94 years). A PD-L1 TPS ≥1% was observed in 52.5% of the entire cohort; regarding specific predominant histological patterns, a PD-L1 TPS ≥1 was documented in 31.2% of patients with predominant-lepidic pattern, 46.2% of patients with predominant-acinar pattern, 42.8% of patients with a predominant-papillary pattern, and 68.7% of patients with predominant-solid pattern (p = 0.002). On the other hand, proportion of tumors with PD-L1 TPS ≥50% was not significantly different among adenocarcinoma subtypes. At the univariate survival analysis, a PD-L1 TPS cut-off value of ≥15% was associated with a worse PFS and OS. Conclusion: According to IASLC/ATS/ERS lung adenocarcinoma classification, the predominant-solid pattern is associated with a higher proportion of PD-L1 positive samples, no subtype was identified to be associated with a high (≥50%) TPS PD-L1.

Cruz-Rico G ，Avilés-Salas A ，Popa-Navarro X ，Lara-Mejía L ，Catalán R ，Sánchez-Reyes R ，López-Sánchez D ，Cabrera-Miranda L ，Aquiles Maldonado-Martínez H ，Samtani-Bassarmal S ，Arrieta O ... -  《-》