Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status

Background The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. Methods We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. Results Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. Conclusions Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.