Y Kobayashi1, T Mitsudomi2, Y Sakao3, Y Yatabe4. 1. Department of Thoracic Surgery, Kinki University Faculty of Medicine, Osaka-Sayama; Department of Thoracic Surgery. 2. Department of Thoracic Surgery, Kinki University Faculty of Medicine, Osaka-Sayama. 3. Department of Thoracic Surgery. 4. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: yyatabe@aichi-cc.jp.
Abstract
BACKGROUND: Pulmonary ground-glass nodules (GGNs) include both malignant and benign lesions. Some GGNs become larger, whereas others remain unchanged for years. We have previously reported that smoking history and large diameters are predictors for growth. However, the genetic differences among GGNs remain unclear. PATIENTS AND METHODS: GGNs with ground-glass component of ≥50% on a thin-section computed tomography scan that were resected between 2012 and 2014 were evaluated for clinicopathological features and the presence of EGFR/KRAS/ALK/HER2 mutations. 'Incidence of 2-mm growth' and 'Time to 2-mm growth' were analyzed according to the mutational status. RESULTS: Among 104 GGNs in 96 patients, this study included 3 atypical adenomatous hyperplasia (AAH), 19 adenocarcinoma in situ (AIS), 27 minimally invasive adenocarcinoma (MIA), and 55 invasive adenocarcinoma (IA). Among the 71 lesions evaluable for growth, 30 GGNs exhibited growth and 5 lesions remained unchanged for ≥2 years before surgery was carried out. We identified mutations or rearrangements in 75% of GGNs (78/104). EGFR mutations were noted in 64% of samples, KRAS in 4%, ALK in 3%, and HER2 in 4%. The remaining 26 quadruple-negative tumors were significantly associated with AAH/AIS (P < 0.01) and no-growth (P < 0.01) compared with driver mutation-positive tumors, whereas EGFR mutation-positive tumors were correlated with MIA/IA (P < 0.01) and growth (P < 0.01) compared with EGFR-negative tumors. CONCLUSIONS: Three fourths of resected GGNs were positive for EGFR, KRAS, ALK, or HER2 mutations. Quadruple-negative tumors were associated with a lack of GGN growth, whereas EGFR mutation-positive tumors displayed a correlation with growth.
BACKGROUND: Pulmonary ground-glass nodules (GGNs) include both malignant and benign lesions. Some GGNs become larger, whereas others remain unchanged for years. We have previously reported that smoking history and large diameters are predictors for growth. However, the genetic differences among GGNs remain unclear. PATIENTS AND METHODS: GGNs with ground-glass component of ≥50% on a thin-section computed tomography scan that were resected between 2012 and 2014 were evaluated for clinicopathological features and the presence of EGFR/KRAS/ALK/HER2 mutations. 'Incidence of 2-mm growth' and 'Time to 2-mm growth' were analyzed according to the mutational status. RESULTS: Among 104 GGNs in 96 patients, this study included 3 atypical adenomatous hyperplasia (AAH), 19 adenocarcinoma in situ (AIS), 27 minimally invasive adenocarcinoma (MIA), and 55 invasive adenocarcinoma (IA). Among the 71 lesions evaluable for growth, 30 GGNs exhibited growth and 5 lesions remained unchanged for ≥2 years before surgery was carried out. We identified mutations or rearrangements in 75% of GGNs (78/104). EGFR mutations were noted in 64% of samples, KRAS in 4%, ALK in 3%, and HER2 in 4%. The remaining 26 quadruple-negative tumors were significantly associated with AAH/AIS (P < 0.01) and no-growth (P < 0.01) compared with driver mutation-positive tumors, whereas EGFR mutation-positive tumors were correlated with MIA/IA (P < 0.01) and growth (P < 0.01) compared with EGFR-negative tumors. CONCLUSIONS: Three fourths of resected GGNs were positive for EGFR, KRAS, ALK, or HER2 mutations. Quadruple-negative tumors were associated with a lack of GGN growth, whereas EGFR mutation-positive tumors displayed a correlation with growth.
Authors: Marcello Migliore; Mariaconcetta Fornito; Manuela Palazzolo; Alessandra Criscione; Mariapia Gangemi; Francesco Borrata; Paolo Vigneri; Marco Nardini; Joel Dunning Journal: Ann Transl Med Date: 2018-03