Journal Article

Molecular characterization of early-stage lung adenocarcinoma presenting as subsolid nodules in a real-life European cohort

Gallina, Filippo Tommaso, Buglioni, Simonetta, Ambrogi, Vincenzo, Cappelli, Federico, Caterino, Mauro, Forcella, Daniele, Melis, Enrico, Visca, Paolo, Vidiri, Antonello, Patirelis, Alexandro, Cecere, Fabiana Letizia, Cappuzzo, Federico, Alessandrini, Gabriele, Fusco, Francesca, Tajè, Riccardo

2025

Overview

Objectives Subsolid nodules emerged as frequent radiological variants of lung adenocarcinoma. Radiological features including solid-component prevalence and larger tumour dimensions prompt tumoral invasiveness guiding prognosis and management. Thus, we aimed to clarify the molecular grounds that dictate these radiological appearances and clinical behaviour in a real-life European-cohort. Additionally, following the growing interest toward targeted-therapies in early-stage diseases, we aimed to present real-life epidemiological data of actionable mutations in these patients. Methods In this retrospective single-centre study, targeted next-generation sequencing was performed continuatively in all the resected subsolid lung adenocarcinomas in the period between May 2016 and December 2023. Clinico-radiological data were collected. The genetic landscape of our real-life European subsolid adenocarcinoma population is defined. Common and actionable mutations (frequency > 5%) relation to key clinico-radiological features are evaluated. Results Overall, 156 subsolid adenocarcinomas were analysed. KRAS -mutations, mostly KRAS p.G12C , were the most prevalent followed by EGFR , including 25% uncommon EGFR -mutations, TP53 and MET mutations. Amongst the clinico-radiological variables, KRAS -mutations and KRAS p.G12C -mutation were associated to smoking history (≥ 20 pack/years), aggressive histologic subtype and higher consolidation-to-tumor ratio (CTR). Moreover, KRAS -mutated nodules had faster tumour-doubling-time. Conversely, EGFR -mutations were associated to female sex and lower CTR. The latter not being confirmed in common EGFR -mutations. Additionally, in common EGFR -mutated nodules, aggressive histological components were rarer. Conclusion Our study presents the molecular profile of subsolid lung adenocarcinoma in a real-life European-cohort. KRAS -mutations were the most prevalent, and were related to smoking history, higher CTR and faster growth. Conversely, common EGFR -mutations were rarer than expected and unrelated to smoking history and radiological features.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma / Adenocarcinoma of Lung - diagnostic imaging / Adenocarcinoma of Lung - epidemiology / Adenocarcinoma of Lung - genetics / Adenocarcinoma of Lung - pathology / Aged / Aged, 80 and over / Analysis / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Diagnosis / DNA sequencing / Early stage lung cancer / Epidemiology / Epidermal growth factor receptors / ErbB Receptors - genetics / Europe - epidemiology / Female / Gene mutations / Genetic aspects / Ground glass / Health aspects / Health Promotion and Disease Prevention / High-Throughput Nucleotide Sequencing / Humans / Invasiveness / Lung cancer / Lung Neoplasms - diagnostic imaging / Lung Neoplasms - epidemiology / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Male / Medical imaging / Medicine/Public Health / Middle Aged / Molecular biology / Molecular characterization / Mutation / Neoplasm Staging / Next generation sequencing / Nodules / Nucleotide sequencing / Oncology / p53 Protein / Proto-Oncogene Proteins p21(ras) - genetics / Retrospective Studies / Smoking / Subsolid nodules / Surgery / Surgical Oncology / Tomography / Tumor proteins / Tumor Suppressor Protein p53 / Tumors