title: Advanced lung adenocarcinomas with ROS1-rearrangement frequently show hepatoid cell.
abstract: Defining distinctive histologic characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) may help identify cases that merit molecular testing. However, the majority of previous reports have focused on surgical specimens but only limited studies assessed histomorphology of advanced NSCLCs. In order to identify the clinical and histological characteristics of ROS1-rearranged advanced NSCLCs, we examined five hundred sixteen Chinese patients with advanced NSCLCs using ROS1 fluorescence in situ hybridization and real-time polymerase chain reaction and then analyzed for clinical and pathological features. We performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement. 19 tumors were identified with ROS1 rearrangement (3.7% of adenocarcinomas). 16 ROS1+ and 122 ROS1- samples with available medical records and enough tumor cells were included for histological analysis. Compared with ROS1-negative advanced NSCLCs,ROS1-rearranged advanced NSCLCs were associated with a younger age at presentation. ROS1 rearrangements were not significantly associated with sex, smoking history, drinking history and metastatic sites. The most common histological pattern was solid growth (12/16), followed by acinar (4/16) growth. 66.7% cases with solid growth pattern showed hepatoid cytology (8/12) and 75% cases with acinar growth pattern showed a cribriform structure (3/4). 18.8% cases were found to have abundant extracellular mucus or signet-ring cells (3/16). Only one case with solid growth pattern showed psammomatous calcifications. In conclusion, age, hepatoid cytology and cribriform structure are the independent predictors for ROS1-rearranged advanced NSCLCs, recognizing these may be helpful in finding candidates for genomic alterations, especially when available tissue samples are limited.
authors.affiliation: Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Kong
authors.affiliation: Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jianya
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D022781:Hepatocytes; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
keywords: NSCLCs; ROS1 rearrangement; biopsy; clinicopathological features