title: Clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma.
  
  
  METHODS
  One hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC).
  
  
  RESULTS
  ROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (-) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377-0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples.
  
  
  CONCLUSIONS
  ROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. kyunghunlee@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. kyunghunlee@snu.ac.kr.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. kblee@snuh.org.
authors.forename: Kyoung-Bun
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. ktyongmd@gmail.com.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. ktyongmd@gmail.com.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. saewonhan@gmail.com.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. saewonhan@gmail.com.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. ohdoyoun@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. ohdoyoun@snu.ac.kr.
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. moisa@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. moisa@snu.ac.kr.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. kimty@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. kimty@snu.ac.kr.
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. gsleenj@hanmail.net.
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Yi
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. kwleegs@gmail.com.
authors.forename: Kwang-Woong
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. kssuh@snu.ac.kr.
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Suh
authors.affiliation: Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. tripj@snu.ac.kr.
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. bangyj@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. bangyj@snu.ac.kr.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human