ONCOmmunity

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

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

BioMed Central
2025-04-09; doi: 10.1186/s12885-025-13998-0

Abstract

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.