Prevalence and clinico-morphological correlates of STK11 mutations in a large cohort of NSCLC lung adenocarcinomas

STK11-mutated non-small cell lung cancers (NSCLC) show distinct clinicopathologic features, often with co-occurring KRAS and TP53 mutations that drive more aggressive disease. This study investigates the mutational landscape and clinical characteristics of STK11-mutated lung adenocarcinomas. We retrospectively reviewed 1,068 primary lung cancer cases from 2018 to 2022, identifying 14 STK11-mutant lung adenocarcinomas. We collected clinicopathologic data (demographics, histology, treatment), performed genomic profiling for co-mutations, and used immunohistochemistry to evaluate associated phenotypes. Patients with STK11 mutations (median age 67) were predominantly male smokers. KRAS or TP53 co-mutations appeared in 50% of cases. STK11/KRAS tumors showed higher metastatic rates, while STK11/TP53 tumors had increased necrosis and mitotic activity. Early-stage patients had longer survival, whereas advanced-stage cases faced significantly worse. Those treated with PD-1/PD-L1 inhibitors (Pembrolizumab) had limited benefit, with a median overall survival of 4.1 ± 2.8 months. STK11-mutant NSCLCs-especially with KRAS or TP53 co-mutations-demonstrate aggressive behavior and poor response to current immunotherapies. Comprehensive genomic profiling may help refine understanding of tumour biology and potentially inform treatment decisions. Larger studies are needed to validate these findings, but integrating genomic, pathologic, and clinical data may advance personalized therapy for these patients.