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

Authors

Dong Woog Yoon, Soohyun Hwang, Boram Lee, Yeong Jeong Jeon, Junghee Lee, Dong Wook Shin, Byeong-Ho Jeong, Seong Yong Park, Hong Kwan Kim, Yong Soo Choi, Jong Ho Cho

Published in

Cancer treatment and research communications. Volume 45. Pages 101014. Oct 08, 2025. Epub Oct 08, 2025.

Abstract

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.

PMID:
41101001
Bibliographic data and abstract were imported from PubMed on 17 Oct 2025.

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