Clinical significance of concurrent TP53 mutations in KRAS-mutant invasive mucinous adenocarcinoma patients undergoing curative-intent lung surgery

Invasive mucinous adenocarcinoma (IMA) is genetically distinct from non-mucinous adenocarcinoma, commonly characterized by KRAS mutations. However, studies exploring molecular co-alterations alongside KRAS mutations in IMA remain limited.

We reviewed 84 patients with surgically resected IMAs from 2015 to 2023 who underwent NGS using TruSight™ Oncology 500 or CancerSCAN assays. Overall survival (OS) and disease-free survival (DFS) were assessed using Cox regression, and log-rank tests were used to evaluate the prognostic role of each molecular alteration.

Among the 84 patients, driver alterations were identified in KRAS (67.9 %, n = 57), ERBB2 (10.7 %, n = 9), and NRG-1 (7.1 %, n = 6), while concurrent mutations were found in TP53 (31 %, n = 26), NKX2-1 (23.8 %, n = 20), CDKN2A (15.5 %, n = 13), and PIK3CA (10.7 %, n = 9). Among the overall cohort, survival analysis demonstrated that TP53 alterations were associated with worse OS (p = 0.03), while NKX2-1 alterations were linked to better DFS (p = 0.03). In the KRAS-mutant subgroup, TP53 alterations were associated with worse OS (p < 0.01) and DFS (p < 0.01), while NKX2-1 mutations were associated with better OS (p = 0.05). Multivariate analysis identified TP53 alterations as independent prognostic factors for OS (HR,11.32; 95 % CI,2.18-58.75) and DFS (HR,4.33; 95 % CI,1.84-10.2) in patients with KRAS mutations.

Concurrent TP53 mutations have significant prognostic implications in KRAS-mutant IMAs. This finding underscores the potential role of TP53 mutations in guiding personalized treatment approaches to improve patient outcomes.

In a retrospective cohort of 84 resected pulmonary invasive mucinous adenocarcinomas, next-generation sequencing was performed and genomic alterations were correlated with prognosis. KRAS was the predominant driver (∼68 %), and concurrent TP53 mutations (∼32 %) independently predicted worse overall and disease-free survival within KRAS-mutant IMA. TP53 co-mutation serves as a practical risk stratifier to inform closer post-surgical surveillance and potential adjuvant strategies.