Shinya Katsumata1, Keiju Aokage2, Tomohiro Miyoshi2, Kenta Tane2, Hiroshi Nakamura3, Masato Sugano4, Motohiro Kojima5, Satoshi Fujii5, Takeshi Kuwata4, Atsushi Ochiai6, Ryuichi Hayashi7, Masahiro Tsuboi2, Genichiro Ishii8. 1. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan; Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan. 2. Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 3. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan; Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 4. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 5. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. 6. Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. 7. Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 8. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. Electronic address: gishii@east.ncc.go.jp.
Abstract
OBJECTIVE: Lepidic growth is a noninvasive component of lung adenocarcinoma. Many adenocarcinoma cases contain coexistent lepidic and nonlepidic (invasive) components (lepidic-growth positive [Lep+] adenocarcinoma); however, some cases comprise only nonlepidic components (lepidic-growth negative [Lep-] adenocarcinoma). The aim of this study was to investigate the biological differences between the invasive components of Lep+ and Lep- adenocarcinoma. METHODS: We investigated the clinicopathologic characteristics of 232 adenocarcinomas (116 size-matched tumor pairs from Lep+ and Lep- adenocarcinomas). We then evaluated the cancer cell-specific expression levels of cancer stem cell, hypoxia, and invasion molecules in these lesions. The number of tumor-promoting stromal cells, including podoplanin-positive cancer-associated fibroblasts and CD204-positive tumor-associated macrophages, was also analyzed. RESULTS: Among cases with size-matched invasive components, significant differences were shown in total tumor size and predominant subtype in invasive component between Lep+ and Lep- adenocarcinomas. The expression levels of hypoxia-related molecules were significantly lower in Lep+ adenocarcinomas (glucose transporter 1: 0 vs 10, P < .01; carbonic anhydrase IX: 0 vs 0 [mean, 4.7 vs 14.1], P = .01). The number of podoplanin-positive cancer-associated fibroblasts and CD204-positive tumor-associated macrophages was significantly lower in Lep+ adenocarcinomas (podoplanin-positive cancer-associated fibroblasts: 0 vs 0 [mean: 1.6 vs 11.6], P < .01; CD204-positive tumor-associated macrophages: 8.7 vs 24.7, P < .01). CONCLUSIONS: Our results indicated that lower cancer cell-specific expression levels of hypoxia markers and a smaller number of tumor-promoting stromal cells in invasive component were characteristic features of Lep+ adenocarcinomas.
OBJECTIVE: Lepidic growth is a noninvasive component of lung adenocarcinoma. Many adenocarcinoma cases contain coexistent lepidic and nonlepidic (invasive) components (lepidic-growth positive [Lep+] adenocarcinoma); however, some cases comprise only nonlepidic components (lepidic-growth negative [Lep-] adenocarcinoma). The aim of this study was to investigate the biological differences between the invasive components of Lep+ and Lep- adenocarcinoma. METHODS: We investigated the clinicopathologic characteristics of 232 adenocarcinomas (116 size-matched tumor pairs from Lep+ and Lep- adenocarcinomas). We then evaluated the cancer cell-specific expression levels of cancer stem cell, hypoxia, and invasion molecules in these lesions. The number of tumor-promoting stromal cells, including podoplanin-positive cancer-associated fibroblasts and CD204-positive tumor-associated macrophages, was also analyzed. RESULTS: Among cases with size-matched invasive components, significant differences were shown in total tumor size and predominant subtype in invasive component between Lep+ and Lep- adenocarcinomas. The expression levels of hypoxia-related molecules were significantly lower in Lep+ adenocarcinomas (glucose transporter 1: 0 vs 10, P < .01; carbonic anhydrase IX: 0 vs 0 [mean, 4.7 vs 14.1], P = .01). The number of podoplanin-positive cancer-associated fibroblasts and CD204-positive tumor-associated macrophages was significantly lower in Lep+ adenocarcinomas (podoplanin-positive cancer-associated fibroblasts: 0 vs 0 [mean: 1.6 vs 11.6], P < .01; CD204-positive tumor-associated macrophages: 8.7 vs 24.7, P < .01). CONCLUSIONS: Our results indicated that lower cancer cell-specific expression levels of hypoxia markers and a smaller number of tumor-promoting stromal cells in invasive component were characteristic features of Lep+ adenocarcinomas.
Authors: David B Nelson; Kyle G Mitchell; Jing Wang; Junya Fujimoto; Myrna Godoy; Carmen Behrens; Xiaofeng Zheng; Jianjun Zhang; Boris Sepesi; Ara A Vaporciyan; Wayne L Hofstetter; Reza J Mehran; David C Rice; Garrett L Walsh; Stephen G Swisher; Cesar A Moran; Neda Kalhor; Annikka Weissferdt; Ignacio I Wistuba; Jack A Roth; Mara B Antonoff Journal: J Thorac Dis Date: 2020-03 Impact factor: 3.005