title: The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology.
abstract: BACKGROUND
  Intrahepatic cholangiocarcinoma (ICC) often is a diagnosis determined by exclusion. Distinguishing ICC from other metastatic adenocarcinomas based on histopathologic or immunohistochemical analysis often is difficult and requires an extensive workup. This study aimed to determine whether albumin, whose expression is restricted to the liver, has potential as a biomarker for ICC using a novel and highly sensitive RNA in situ hybridization (ISH) platform.
  
  
  METHODS
  Modified branched DNA probes were developed for albumin RNA ISH. The study evaluated 467 patient samples of primary and metastatic lesions.
  
  
  RESULTS
  Of the 467 samples evaluated, 83 were ICCs, 42 were hepatocellular carcinomas (HCCs), and 332 were nonhepatic carcinomas including tumors arising from the perihilar region and bile duct, pancreas, stomach, esophagus, colon, breast, ovary, endometrium, kidney, and urinary bladder. Albumin RNA ISH was highly sensitive for cancers of liver origin, staining positive in 82 (99 %) of 83 ICCs and in 42 HCCs (100 %). Perihilar and distal bile duct carcinomas as well as carcinomas arising at other sites tested negative for albumin. Notably, 6 (22 %) of 27 intrahepatic tumors previously diagnosed as carcinomas of undetermined origin tested positive for albumin.
  
  
  CONCLUSIONS
  Albumin RNA ISH is a sensitive and highly specific diagnostic tool for distinguishing ICC from metastatic adenocarcinoma to the liver or carcinoma of unknown origin. Albumin RNA ISH could replace the extensive diagnostic workup, leading to timely confirmation of the ICC diagnosis. Additionally, the assay could serve as a guide to distinguish ICC from perihilar adenocarcinoma.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. CFERRONE@mgh.harvard.edu.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Ting
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.|Division of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ioannis T
authors.initials: IT
authors.lastname: Konstantinidis
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sabbatino
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Lipika
authors.initials: L
authors.lastname: Goyal
authors.affiliation: Division of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Rice-Stitt
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Mubeen
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.|Division of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Arora
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Bardeesey
authors.affiliation: Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: John
authors.initials: J
authors.lastname: Miura
authors.affiliation: Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: T Clark
authors.initials: TC
authors.lastname: Gamblin
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Darrell
authors.initials: D
authors.lastname: Borger
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.affiliation: Division of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Rivera
authors.affiliation: Division of Pathology, Massachusetts General Hospital, Boston, MA, USA. vdeshpande@partners.org.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics; D000368:Aged; D000418:Albumins / Q000235:genetics*; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000418:Albumins; D012333:RNA, Messenger; D004247:DNA