The correlation between EGFR mutation status and clinicopathological characteristics, Ki67 expression and immune cell infiltration in lung adenocarcinoma with different radiological subtypes.

BACKGROUND: To clearly reveal the correlations between epidermal growth factor receptor (EGFR) mutation status and clinicopathological characteristics, Ki67 expression and immune cell Infiltration in lung adenocarcinoma (LUAD) with different radiological subtypes. METHODS: Patients with pathological stage 0-III LUAD who underwent resection and received EGFR detection in our department between July 2019 and May 2023 were retrospectively reviewed. All included patients were divided into four groups based on different consolidation-to-tumour ratio (CTR). Tumors without ground glass opacity (GGO) component were defined as solid nodule featured LUAD (SN-LUAD, CTR = 1) and the other tumors with GGO were defined as GGO featured LUAD (GGO-LUAD, 0 ≤ CTR < 1). The clinicopathological characteristics, Ki67 expression, immune cell infiltration and EGFR mutation status were compared between diferent CTR groups. RESULTS: A total of 544 patients were finally included, 140 in the pure GGO group (PGGO, CTR = 0), 120 in the GGO-dominant group (GGO-D, 0 < CTR ≤ 0.5), 92 in the SN-dominant group (SN-D, 0.5 < CTR < 1), and 192 in the pure solid nodule group (SN, CTR = 1). The rate of EGFR mutations were significantly more higher in elderly patients (P < 0.001), well/moderate differentiated (P < 0.001), invasive (P < 0.001) and large size tumors (P < 0.001). Regardless of gender, smoking status, tumor size, and pathological subtype, the rate of EGFR mutation in GGO-LUAD significantly increases with the decrease of GGO component. Importantly, the expression of Ki67 was significantly correlated with EGFR mutation status in GGO-LUAD, but not in SN-LUAD. In GGO-LUAD, tumors with EGFR mutations have significantly higher Ki67 expression than tumors without. Additionally, SN-LUAD has significantly higher infiltration of tumor associated macrophages and regulatory T cells compared to GGO-LUAD in EGFR mutated LUAD. CONCLUSIONS: EGFR mutation rates vary by clinicopathological characteristics and EGFR mutation status significantly influence tumor proliferation and immune cell infiltration in LUAD across radiological subtypes. These findings not only indicate that EGFR mutations may play a crucial role in the progression of GGO-LUAD, but also explain why GGO-LUAD has a better prognosis.