Definizione del fenotipo clinico del paziente con tumore polmonare non a piccole cellule e mutazione del gene BRAF

This thesis explores the clinical and pathological features of patients diagnosed with non- small cell lung cancer (NSCLC) harboring BRAF mutations. The BRAF gene encodes a serine/threonine kinase involved in the MAPK/ERK signaling pathway, regulating cell growth and survival. BRAF mutations occur in approximately 1-4% of lung adenocarcinomas, with V600E being the most common variant. Clinically, these mutations identify a distinct NSCLC subgroup with specific therapeutic implications, including targeted therapy with BRAF and MEK inhibitors. Conducted as a retrospective analysis, the study encompasses a regional cohort from Veneto (Italy) between 2021 and 2023, including 2314 NSCLC cases, of which 46 tested positive for BRAF mutations. A comparison was made with 56 BRAF wild-type patients who were also negative for other common oncogenic drivers (EGFR, ALK, ROS1, RET, MET). The results show that BRAF mutant patients exhibit partially overlapping characteristic with wild type (WT) patients: a predominance of males, frequent diagnosis at advanced stages, and a prevalent adenocarcinoma histology. However, significant differences emerged: BRAF mutant patients showed a higher expression of PD-L1 (76% vs 51%), a higher frequency of nonspecific symptoms was observed in WT patients, and a greater proportion of symptomatic casas was found among non-V600E BRAF mutants. The V600E mutation was more frequently associated with a symptomatic clinical presentation. A modest difference in respiratory function (total lung capacity) was also observed in favor of BRAF mutant patients. These results emphasize the clinical relevance of early BRAF mutation testing, regardless of tumor stage, as targeted therapies could be beneficial beyond advanced disease. The study offers valuable insights into a rare molecular subtype of NSCLC and underscores the need for prospective validation in larger cohorts.