%0 Journal Article
%T Prognostic value of the international association for the study of lung cancer grading system and its association with the tumor microenvironment in stage I EGFR-muted lung adenocarcinoma.
%A Kubota S
%A Taki T
%A Miyoshi T
%A Tane K
%A Samejima J
%A Aokage K
%A Wakabayashi M
%A Nomura K
%A Nagamine M
%A Kojima M
%A Sakashita S
%A Sakamoto N
%A Tsuboi M
%A Ishii G
%J Eur J Cancer
%V 207
%N 0
%D 2024 Aug 24
%M 38936102
%F 10.002
%R 10.1016/j.ejca.2024.114184
%X <B>BACKGROUND: </B>The International Association for the Study of Lung Cancer (IASLC) grading system predicts early lung adenocarcinoma outcomes.<BR><B>METHODS: </B>The purpose of this study is to examine prognostic value of the IASLC grading system and its association with the tumor microenvironment (TME) in Stage I EGFR-muted lung adenocarcinoma. Based on the IASLC grading system, we compared the clinicopathological characteristics of EGFR-mutated lung adenocarcinoma (n = 296). In addition, we examined the expression level of E-cadherin in tumor cells and counted the number of tumor-infiltrating lymphocytes (TILs; CD8, CD20, CD138, and Foxp3), tumor-associated macrophages (TAMs; CD204), and cancer-associated fibroblasts (CAFs; podoplanin) using semi-automatic digital pathology image analysis.<BR><B>RESULTS: </B>Recurrence-free survival (RFS) curve showed that survival of grade 3 was significantly shorter than that of grade 1 (P < 0.01) and grade 2 (P = 0.03). Multivariate analysis of RFS revealed the invasive size, lymphatic permeation, and grade 3 (P < 0.01) as independent poor prognostic factors. The number of CD204 +TAMs and PDPN+CAFs was significantly higher in grade 3 than in grade 1 or 2 (all P < 0.01). Among the intermediate grade by the predominant subtype based classification, cases classified as grade 3 by the new classification had higher number of CD204 +TAMs (P < 0.01) and PDPN+CAFs (P = 0.02) than those classified as grade 2.<BR><B>CONCLUSIONS: </B>The IASLC grading system correlated with the outcomes of EGFR-mutated lung adenocarcinoma. Grade 3 was found to have the TME that most contributes to tumor progression, which probably explained their poor prognosis.