Prognostic impact of mitosis and necrosis in non-mucinous lung adenocarcinomas and correlation with IASLC grading system

Abstract

Background. In 2020, the International Lung Cancer Study Group (IASLC) Pathology Committee established a grading system for non-mucinous primary lung adenocarcinomas. This grading system is based on whether areas of high-grade patterns are present in more than 20% of the tumor. Parameters, such as necrosis, mitotic activity, lymphovascular invasion (LVI) and spread through air spaces (STAS), are excluded from evaluating the grading system. Methods. A total of 217 patients' lung resection materials for primary lung adenocarcinoma were re-reviewed using the IASLC grading system. Necrosis, mitotic activity, LVI status and STAS were also evaluated in the resection materials, aiming to demonstrate the relationship between these histopathological features and clinical outcome data. Results. At all stages, overall survival (OS) and recurrence-free survival (RFS) were related to grade (p=0.011 and 0.024, respectively). Additionally, patients with necrosis were associated with worse OS and RFS (p=0.002 and 0.048, respectively). When grade 2 and 3 tumors were analyzed individually, a significant relationship was found between necrosis and OS in grade 3 tumors (p=0.002). Patients with a high mitotic count (≥10/10 high-power fields) had significantly worse OS (p=0.046). The prevalence of LVI and STAS increased with grade; however, their prognostic significance has not been demonstrated. Conclusions. The new grading system provides a highly efficient prognostic classification for survival. Necrosis and high mitotic count are important prognostic parameters for survival. Additionally, necrosis is a stage-independent prognostic factor for OS in grade 3 tumors, although no effect on prognosis can be demonstrated in grade 2 tumors.