title: Frequent aerogenous spread with decreased E-cadherin expression of ROS1-rearranged lung cancer predicts poor disease-free survival.
abstract: OBJECTIVE
  ROS1 rearrangement has been found in a subset of lung cancer and ROS1-rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications and histomorphological characteristics of ROS1-rearranged tumors, especially micropapillary and aerogenous spread growth and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement.
  
  
  METHODS
  ROS1 rearrangement characterizations by fluorescence in situ hybridization and ROS1 protein and E-cadherin expression by immunohistochemistry were performed using 754 non-small cell lung cancer surgical specimens.
  
  
  RESULTS
  ROS1 rearrangement was identified in 10 samples. Histologically, all 10 ROS1-rearranged tumors harbored an adenocarcinoma component. Significantly, we noted a high association between ROS1 rearrangement with a micropapillary component (p<0.001), aerogenous spread (p=0.002), and E-cadherin loss (p=0.049). Survival analysis showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence (p=0.024). The best criterion to detect ROS1-rearrangement by immunohistochemistry was an H-score of ≥100, with a sensitivity and specificity of 90% and 93.5%, respectively.
  
  
  CONCLUSIONS
  ROS1-rearranged adenocarcinoma exhibited distinct morphological and clinicopathological features. Decreased membranous E-cadherin expression and aerogenous spread may be associated with worse disease-free survival. ROS1 immunohistochemistry correlated well with ROS1 gene rearrangement.
authors.affiliation: Department of Pathology, Biomedical Research Institute/Experimental Clinical Research Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Pathology, Biomedical Research Institute/Experimental Clinical Research Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Ping-Li
authors.initials: PL
authors.lastname: Sun
authors.affiliation: Department of Pathology, Biomedical Research Institute/Experimental Clinical Research Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea, 110-744, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea, 110-744, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Eunhyang
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea, 110-744, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Gilhyang
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Sukki
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Kwhanmien
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea.
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 463-707, Republic of Korea. Electronic address: chungjh@snu.ac.kr.
authors.forename: Jin-Haeng
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015820:Cadherins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
keywords: Histomorphology; Immunohistochemistry; Lung cancer; ROS1