ArticleTurk patoloji dergisi2026
NGS-Based Mutation Profiling and PD-L1 Expression in NSCLC Patients: A Single-Centre Prospective Analysis.
Article in Turk patoloji dergisi, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveNon-small cell lung cancer (NSCLC) is a molecularly heterogeneous disease in which both actionable mutations and PD-L1 expression influence therapeutic decisions. This study aimed to evaluate the molecular profile of NSCLC using next-generation sequencing (NGS) and analyse the association of PD-L1 expression with key genetic alterations. MATERIAL AND
methodsA retrospective analysis was conducted on 87 histopathologically confirmed NSCLC cases. Molecular profiling was performed using the Oncomine™ Lung Focus Assay, which targets major actionable mutations. PD-L1 expression was assessed by immunohistochemistry (IHC) using the Tumour Proportion Score (TPS) and categorised as < 1% (negative), 1- 49% (weak positive), and ≥50% (strong positive).
resultsA total of 105 molecular alterations were identified across 87 cases, with EGFR being the most frequently mutated gene (36.2%), followed by KRAS (16.2%) and AR amplification (14.3%). Actionable mutations were defined as alterations with approved targeted therapies or clinical trial eligibility were detected in 59.8% of patients, with EGFR exon 19-21 being the most frequent (25.7%), followed by ALK fusions (5.7%), ERBB2 exon 20 (4.8%), KRAS G12C (3.5%), MET exon 14 skipping (2.9%), and BRAF V600E and ROS1 (1.9% each). PD-L1 expression was observed in 45.7% of cases. PD-L1 positivity was lower in EGFR-mutant tumours compared to EGFR wild-type, suggesting reduced immunogenicity in this subgroup. Conversely, KRAS-mutant tumours exhibited higher PD-L1 expression than KRAS wild-type tumours, suggesting a potential predictive role for immunotherapy. ALK-rearranged tumours showed variable but notable PD-L1 expression.
conclusionThe study underscores the importance of integrating NGS-based molecular testing with PD-L1 evaluation for personalised management of NSCLC. Distinct patterns of PD-L1 expression across molecular subtypes, particularly lower in EGFR-mutated tumours and higher in KRAS-mutated tumours, underscore the need for tailored therapeutic strategies and informed sequencing of targeted therapies and immunotherapies.
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