Subtyping of advanced lung cancer based on PD-L1 expression, tumor histopathology and mutation burden (EGFR and KRAS): a study from North India

Submitted: October 4, 2022
Accepted: December 13, 2022
Published: February 1, 2023
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Immune checkpoint inhibitor (PD-L1) therapy of advanced non-small-cell lung cancer (NSCLC) has variable outcomes. Tumor subtypes based on PD-L1 expression, histopathology, mutation burden is required for patient stratification and formulation of treatment guidelines. Lung cancers (n=57) diagnosed at Pathology department, VPCI (2018-2021) were retrospectively analyzed. PD-L1(SP263) expressed by tumor cells [low (<1%), medium (1-49%), high (≥50%)] was correlated with histopathology, microenvironment, EGFR, KRAS expression. Patients were categorized into high and low risk based on their: i) gender: males (n=47, 30-89 years), females (n=10, 45-80 years); ii) smoking history: males 26/47 (45.61%), females 1/10 (10%); iii) tumor subtyping: squamous cell carcinoma 15/57 (26.32%), adenocarcinoma 6/57 (17.54%), NSCLC-undifferentiated 24/57 (42.10%), adenosquamous carcinoma 5/57 (8.77 %), carcinosarcoma 4/57 (7.02%), small cell carcinoma 1/57 (1.75%); iv) inflammatory tumor microenvironment/TILs 44/57 (77.1%); iv) PD-L1 positivity-31/57 (54.3%); v) concomitant EGFR/KRAS positivity. PD-L1positive cases showed squamous/undifferentiated histopathology, concomitant EGFR+ (9/20, 45%) and KRAS+ (8/15, 53.3%), smoking+ (21/31,67.74%).PD-L1 negative cases (26/57, 45.6%), were EGFR+ (2/14, 14.28%) and KRAS+ (6/19, 31.5%). The high-risk lung cancer subtypes show squamous/undifferentiated histopathology, inflammatory microenvironment, male preponderance, smoking history, higher concomitant PD-L1, KRAS and EGFR positivity. Lung cancer subtyping can predict clinical response/resistance of patients prior to initiation of PD-L1 inhibitor therapies and can be used to guide therapy.

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Supporting Agencies

The intramural funding was provided by Vallabhbhai Patel Chest Institute, University of Delhi

How to Cite

Kulshrestha, Ritu, Himanshi Saxena, Raj Kumar, Sonam Spalgais, Parul Mrigpuri, Nitin Goel, Balakrishnan Menon, Meenu Rani, Pawan Mahor, and Ishita Bhutani. 2023. “Subtyping of Advanced Lung Cancer Based on PD-L1 Expression, Tumor Histopathology and Mutation Burden (EGFR and KRAS): A Study from North India”. Monaldi Archives for Chest Disease 93 (4). https://doi.org/10.4081/monaldi.2023.2449.