Histopathologic Features of the Tumor Budding in Adenocarcinoma of the Lung: Tumor Budding As an Index to Predict the Potential Aggressiveness Yoko Yamaguchi,

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Histopathologic Features of the Tumor Budding in Adenocarcinoma of the Lung: Tumor Budding As an Index to Predict the Potential Aggressiveness Yoko Yamaguchi, MD, Genichiro Ishii, MD, Motohiro Kojima, MD, Kiyotaka Yoh, MD, Hajime Otsuka, MD, Yoichi Otaki, MD, Keiju Aokage, MD, Shingo Yanagi, Kanji Nagai, MD, Yutaka Nishiwaki, MD, Atsushi Ochiai, MD Journal of Thoracic Oncology Volume 5, Issue 9, Pages 1361-1368 (September 2010) DOI: 10.1097/JTO.0b013e3181eaf2f3 Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Histologic features of tumor budding. A, Tumor budding in the area of fibrosis (hematoxylin and eosin [HE] staining). B, Moderate magnification of the area boxed in A: budding cells (BCs) are observed in the fibrotic stroma (HE staining). C, Higher magnification of the area boxed in A. Tumor budding is visible in the form of isolated small clusters or single invading carcinoma cells with eosinophilic cytoplasm (HE staining). D, Cytokeratin AE1/3 immunostaining of BCs. Journal of Thoracic Oncology 2010 5, 1361-1368DOI: (10.1097/JTO.0b013e3181eaf2f3) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Cumulative overall survival curves. A, Cumulative overall survival curves of 181 patients stratified by the presence or absence of tumor budding. B, Cumulative overall survival curves of 181 patients stratified by grade of tumor budding. Journal of Thoracic Oncology 2010 5, 1361-1368DOI: (10.1097/JTO.0b013e3181eaf2f3) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Differences in the immunostaining for β-catenin, E-cadherin, laminin-5γ2, and SP-A. A, β-catenin staining: decreased membrane immunostaining was found in BC (arrows) compared with tumor cells forming solid nests. B, E-cadherin staining: decreased membrane immunostaining was found in BC (arrows) compared with tumor cells forming solid nests. C, Laminin-5γ2 staining: increased cytoplasm immunostaining was found in BC (arrows) compared with tumor cells forming solid nests. D, SP-A staining: decreased cytoplasm immunostaining was found in BC (arrows) compared with tumor cells forming solid nests. Journal of Thoracic Oncology 2010 5, 1361-1368DOI: (10.1097/JTO.0b013e3181eaf2f3) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions