Tomohiro Ichikawa1, Koichi Saruwatari2, Sachiyo Mimaki3, Masato Sugano4, Keiju Aokage5, Motohiro Kojima4, Tomoyuki Hishida5, Satoshi Fujii4, Junji Yoshida5, Takeshi Kuwata4, Atsushi Ochiai4, Kenji Suzuki6, Masahiro Tsuboi5, Koichi Goto2, Katsuya Tsuchihara3, Genichiro Ishii7. 1. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Japan; Division of Thoracic Surgery, National Cancer Center Hospital East, Japan; Department of General Thoracic Surgery, Juntendo University School of Medicine, Japan. 2. Division of Thoracic Oncology, National Cancer Center Hospital East, Japan. 3. Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Japan. 4. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Japan. 5. Division of Thoracic Surgery, National Cancer Center Hospital East, Japan. 6. Department of General Thoracic Surgery, Juntendo University School of Medicine, Japan. 7. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Japan. Electronic address: gishi@east.ncc.go.jp.
Abstract
INTRODUCTION: Lung cancer mimicking organizing pneumonia (LCOP) is a novel radiological entity of lung adenocarcinoma that could be misdiagnosed as inflammatory lesions. However, the characteristic biological and genetic features of LCOP are not fully clarified. MATERIALS AND METHODS: We used thin-section CT images to select cases of (LCOP) among surgically resected lung adenocarcinoma patients. We compared the clinicopathological characteristics and the immunophenotypes of LCOP (n=44) and other lepidic-predominant adenocarcinomas (non-LCOP, n=56). We also analyzed the genomic mutation features of LCOP (n=4) by whole-exome sequencing (WES). RESULTS: All LCOP lesions were lepidic-predominant invasive adenocarcinoma. Patients with LCOP had significantly superior recurrence-free survival, compared to non-LCOP patients (95.5% and 74.4%; P=0.006, respectively). Vascular invasion and lymph node metastasis were less frequent in LCOP than in non-LCOP patients (P=0.001 and P=0.03, respectively). The cancer cell expression levels of aggressiveness-related molecules, including ezrin, ALDH-1, laminin-5 were similar between LCOP and non-LCOP. On the contrary, the number of tumor promoting stromal cells, i.e., podoplanin-positive cancer-associated fibroblasts and CD204-positive tumor associated macrophages, was significantly lower in LOCP (P=0.021 and P=0.037, respectively). WES revealed that ABCB1, DNAH3, MSI2, and SLITRK2 were specifically mutated in LCOP. CONCLUSIONS: Our results indicate that LCOP is characterized by fewer tumor-promoting stromal cells, which may contribute to the better prognosis of LCOP patients. Moreover, recognition of specific somatic mutations of LCOP patients may provide information regarding the development and progression of this type of lung cancer.
INTRODUCTION:Lung cancer mimicking organizing pneumonia (LCOP) is a novel radiological entity of lung adenocarcinoma that could be misdiagnosed as inflammatory lesions. However, the characteristic biological and genetic features of LCOP are not fully clarified. MATERIALS AND METHODS: We used thin-section CT images to select cases of (LCOP) among surgically resected lung adenocarcinomapatients. We compared the clinicopathological characteristics and the immunophenotypes of LCOP (n=44) and other lepidic-predominant adenocarcinomas (non-LCOP, n=56). We also analyzed the genomic mutation features of LCOP (n=4) by whole-exome sequencing (WES). RESULTS: All LCOP lesions were lepidic-predominant invasive adenocarcinoma. Patients with LCOP had significantly superior recurrence-free survival, compared to non-LCOP patients (95.5% and 74.4%; P=0.006, respectively). Vascular invasion and lymph node metastasis were less frequent in LCOP than in non-LCOP patients (P=0.001 and P=0.03, respectively). The cancer cell expression levels of aggressiveness-related molecules, including ezrin, ALDH-1, laminin-5 were similar between LCOP and non-LCOP. On the contrary, the number of tumor promoting stromal cells, i.e., podoplanin-positive cancer-associated fibroblasts and CD204-positive tumor associated macrophages, was significantly lower in LOCP (P=0.021 and P=0.037, respectively). WES revealed that ABCB1, DNAH3, MSI2, and SLITRK2 were specifically mutated in LCOP. CONCLUSIONS: Our results indicate that LCOP is characterized by fewer tumor-promoting stromal cells, which may contribute to the better prognosis of LCOP patients. Moreover, recognition of specific somatic mutations of LCOP patients may provide information regarding the development and progression of this type of lung cancer.