{Reference Type}: Journal Article
{Title}: 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.
{Author}: Kubota S;Taki T;Miyoshi T;Tane K;Samejima J;Aokage K;Wakabayashi M;Nomura K;Nagamine M;Kojima M;Sakashita S;Sakamoto N;Tsuboi M;Ishii G;
{Journal}: Eur J Cancer
{Volume}: 207
{Issue}: 0
{Year}: 2024 Aug 24
{Factor}: 10.002
{DOI}: 10.1016/j.ejca.2024.114184
{Abstract}: <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.