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	Extranodal extension in lung adenocarcinoma: pathological insights and its implication as a histological marker of clinical aggressiveness.
掲載誌名	正式名：British journal of cancer 略　 称：Br J Cancer ISSNコード：15321827/00070920
掲載区分	国外
巻・号・頁	134(4),pp.567-576
著者・共著者	Shunta Tsuchida, Tetsuro Taki, Kotaro Nomura, Kazushi Suzuki, Hiroko Hashimoto, Shoko Kubota, Tomohiro Miyoshi, Kenta Tane, Yuki Matsumura, Joji Samejima, Keiju Aokage, Masashi Wakabayashi, Yukiko Sasahara, Michiko Nagamine, Shingo Sakashita, Naoya Sakamoto, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
発行年月	2026/02
概要	BACKGROUND:Extranodal extension (ENE) is a recognized adverse prognostic factor in several malignancies, but its pathological basis and clinical significance in lung adenocarcinoma (LUAD) remain poorly understood.METHODS:We retrospectively analyzed 105 patients with N1/N2 LUAD who underwent anatomical resection between 2016 and 2020. AI-assisted image analysis quantified tumor-infiltrating lymphocytes (CD8 + , FoxP3 + ), tumor-associated macrophages (CD204 + ), and cancer-associated fibroblasts (CAFs; podoplanin + ) and measured areas of cancer cells and fibrous stroma. In vitro, the effect of CAF quantity on A549 cell invasion was evaluated. Prognostic relevance of ENE was assessed using multivariate and cumulative incidence analyses.RESULTS:While primary tumors showed no significant differences in immune or stromal composition, ENE-positive metastatic nodes exhibited a markedly larger fibrous stroma area than ENE-negative nodes (14.2 vs. 4.0 mm², p < 0.001). In vitro, the invasion distance of A549 cells increased when cocultured with higher numbers of CAFs. Clinically, ENE independently predicted poorer overall survival (p = 0.04) and was associated with a higher incidence of distant metastasis in both multivariate (p = 0.03) and cumulative incidence analyses (p = 0.02).CONCLUSIONS:ENE represents a pathological prognostic factor characterized by abundant fibrous stroma. It independently predicts distant metastasis and may warrant consideration as a qualitative parameter in N classification for lung adenocarcinoma.
DOI	10.1038/s41416-025-03272-2
PMID	41402558