KRAS G12C 突变肺腺癌的形态学和分子特征

Lung adenocarcinoma (LUAD) is the major subtype of non-small cell lung cancer, accounting for approximately 60% of cases. Molecular analysis of LUADs showed that the KRAS gene is mutated in up to 30% of cases; such cases were previously considered "undruggable". The KRAS G12C mutation has become a hot topic of research after initial, promising, phase I and II trials with targeted inhibitors.

We analyzed the morphological and genomic landscape of 202 KRAS G12C mutated LUADs using next-generation sequencing, and identified a specific subtype of patients that could show an improved response to KRAS G12C inhibitors. The main histological subtype was acinar in 29. 7% of cases. Tumor-infiltrating lymphocytes (TILs) were highly or moderately abundant in more than 60% of cases. The immunohistochemical profile showed TTF1 positivity in 78.

7% of cases and PD-L1 positivity in 44. 1% of cases. The molecular profile showed an association between KRAS G12C and STK11 mutations in 25. 2% of cases. This subgroup was associated with a statistically significant lower TTF1 ( p = 0. 0092) and PD-L1 ( p < 0. 0001) positivity. This type of combined morphological and molecular analysis can improve our understanding of tumor biology, and help us to identify specific patient subgroups that can achieve the best treatment response.