부산대학교 도서관

Background: TP53 mutation is present in about 50.8% of lung adenocarcinomas, frequently in combination with other genetic alterations. However, a rare subset harbors the TP53 mutation alone. Methods: Next-generation sequencing was performed in 844 lung adenocarcinomas diagnosed by fine needle aspiration. Fourteen cases (1.7%) showed isolated TP53 alteration and were subjected to a comprehensive analysis. Results: The average age at diagnosis was 65.7 years (range 48–79); 9 males and 5 females. All were smokers with an average pack-year of 40.7 (range 10–70). Ten had metastases, mostly in the brain (n=4) and pleura (n=4). After a followup period of up to 102months, 9 died, 3 were alive free of disease, 1 was alive with disease, and 1 was lost to follow-up. The median survival was 12.2months. Most tumors exhibited poor differentiation, composed of solid sheets with moderate to severe atypia, increased mitotic activity, and necrotic background. Half were positive for TTF-1 and showed p53 overexpression. PD-L1 was positive in 5 cases. Most alterations were missense mutations in exons 5–8, and this mutation type was associated with p53 overexpression. Tumors with combined missense mutation and truncated protein had higher PD-L1 expression along with a trend towards an increase in tumor mutational burden (TMB). CEBPA deletion of undetermined significance was the most common copy number alteration. Conclusion: Isolated TP53 mutation was seen in association with smoking, high-grade cytomorphologic features, adverse prognosis, and recurrent CEBPA deletions. These tumors tend to have strong PD-L1 expression and high TMB, suggesting potential benefit from immune checkpoint inhibitors. Hence, the recognition of this molecular group has prognostic and therapeutic implications. [ABSTRACT FROM AUTHOR]