KRAS G12C is Less Common in Primary Lung Mucinous Adenocarcinoma

Summary: Introduction: Primary lung mucinous adenocarcinoma (PLMAC) commonly harbors KRAS mutations. However, the frequency of different KRAS variants in PLMAC has rarely been reported. We aim to investigate the KRAS mutational profile in PLMAC. Materials and Methods: Our pathology archives were searched to identify PLMAC cases (2018 - 2022) and primary lung non-mucinous adenocarcinoma (PLNMAC) cases (October – December 2022). Corresponding molecular results, patient demographics, and smoking status were recorded. Statistical analysis was performed using an online Z-Score calculator. Results: A total of 117 patients with PLMAC were identified (65F:52M, mean age 70 years, range 37-93 years), with 27 (23%) of them being never smokers. A total of 185 patients with PLNMAC were included (116F:69M, mean age 69 years, range 47-93 years), with 26 (14%) of them being never smokers. Table 1 lists the molecular results. In the PLMAC cohort, 62 out of 86 (72%) patients had KRAS mutations (Table 2). KRAS variants included G12V (n = 24, 39%), G12D (n = 20, 32%), G12C (n = 12, 19%), and others (n = 6, 10%). Twelve out of 16 (71%) never smokers had KRAS mutations, and KRAS G12C was not identified. In the PLNMAC cohort, 61 out of 154 (40%) patients had KRAS mutations. KRAS variants were G12C (n = 29, 47%), G12V (n = 14, 23%), G12D (n = 6, 10%), and others (n= 12, 20%). Only one never smoker had a KRAS mutation, which was G12C. Conclusions: PLMAC had significantly fewer KRAS G12C mutations than PLNMAC (19% vs. 47%, p < 0.05) and KRAS G12C mutation was not detected in the never smokers, indicating that patients with PLMAC would be less likely to benefit from KRAS G12C targeted therapy. The value of using KRAS G12C to distinguish PLMAC from mucinous adenocarcinoma of other organ sites was limited, as only 1/5 of PLMAC cases had this variant.