クボタ　ショウコ   KUBOTA Shouko   久保田　晶子    所属   医学部 医学科（附属足立医療センター）    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Solid Predominant Histology and High Podoplanin Expression in Cancer-Associated Fibroblast Predict Primary Resistance to Osimertinib in EGFR-Mutated Lung Adenocarcinoma.
掲載誌名	正式名：JTO clinical and research reports 略　 称：JTO Clin Res Rep ISSNコード：26663643/26663643
掲載区分	国外
巻・号・頁	6(3),pp.100779
著者・共著者	Yuji Uehara, Hiroki Izumi, Tetsuro Taki, Tetsuya Sakai, Hibiki Udagawa, Eri Sugiyama, Shigeki Umemura, Yoshitaka Zenke, Shingo Matsumoto, Kiyotaka Yoh, Shoko Kubota, Keiju Aokage, Naoya Sakamoto, Shingo Sakashita, Motohiro Kojima, Michiko Nagamine, Yukio Hosomi, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii
発行年月	2025/03
概要	INTRODUCTION:Resistance to EGFR tyrosine kinase inhibitors is influenced by tumor-intrinsic and -extrinsic factors. We investigated the impact of tumor cell histology and tumor microenvironment on the efficacy of osimertinib.METHODS:We evaluated surgically resected adenocarcinoma from patients treated with first-line osimertinib at the National Cancer Center Hospital East (2016-2023), evaluating clinicopathologic characteristics, tumor cell histology, podoplanin expression in cancer-associated fibroblasts (CAFs) identified by immunohistochemistry, and outcomes. We also investigated HGF mRNA expression levels, using The Cancer Genome Atlas Program and Singapore Oncology Data Portal cohorts.RESULTS:The study included 93 patients. Solid (n = 19) versus non-solid predominant (n = 74) histology was not associated with worse disease-free survival after surgery (p = 0.12), but was significantly associated with worse progression-free survival (PFS) and overall survival following osimertinib treatment (p = 0.026, p = 0.004). Similarly, high-podoplanin (n = 31) versus low-podoplanin (n = 62) expression in CAFs was not associated with worse disease-free survival after surgery (p = 0.65), but was significantly associated with worse PFS and showed a trend towards worse overall survival following osimertinib treatment (p < 0.001, p = 0.11). In the multivariable analysis, solid predominant histology and high-podoplanin expression in CAFs were independently associated with worse PFS. In the cohorts of The Cancer Genome Atlas Program and Singapore Oncology Data Portal, EGFR-mutated lung adenocarcinoma with solid predominant histology or high-podoplanin expression exhibited significantly higher HGF expression.CONCLUSIONS:Solid predominant histology and high-podoplanin expression in CAFs predicted osimertinib resistance, potentially guiding the selection of patients for more intensive treatments beyond osimertinib monotherapy.
DOI	10.1016/j.jtocrr.2024.100779
PMID	40007550