Yunjian Pan1, Yang Zhang1, Yuan Li2, Haichuan Hu1, Lei Wang1, Hang Li1, Rui Wang1, Ting Ye1, Xiaoyang Luo1, Yiliang Zhang1, Bin Li1, Deng Cai1, Lei Shen2, Yihua Sun3, Haiquan Chen4. 1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. 3. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: Sun_yihua76@hotmail.com. 4. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: hqchen@yahoo.com.
Abstract
BACKGROUND: To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas. METHODS: Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations. RESULTS: There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P = 0.007), whereas all the 15 tumors harboring RET fusions were ≤ 3 cm in diameter (P = 0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P < 0.001), cribriform pattern (P < 0.001), signet ring cells (P < 0.001) and hepatoid cytology (P < 0.001). No significant difference in relapse-free survival (P = 0.147) and overall survival (P = 0.444) was observed between fusion-positive and fusion-negative patients. CONCLUSIONS: This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.
BACKGROUND: To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas. METHODS: Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinomapatients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations. RESULTS: There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P = 0.007), whereas all the 15 tumors harboring RET fusions were ≤ 3 cm in diameter (P = 0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P < 0.001), cribriform pattern (P < 0.001), signet ring cells (P < 0.001) and hepatoid cytology (P < 0.001). No significant difference in relapse-free survival (P = 0.147) and overall survival (P = 0.444) was observed between fusion-positive and fusion-negative patients. CONCLUSIONS: This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.
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