Rare Incidence ofROS1Rearrangement in Cholangiocarcinoma.
OBJECTIVE
The recent discovery and characterization of an oncogenicROS1gene rearrangement has raised significant interest because small molecule inhibitors are effective in these tumors. The aim of this study was to determine frequency and clinicopathological features associated withROS1rearrangement in patients with cholangiocarcinoma (CCA).


METHODS
A total of 261 patients who underwent surgery for CCA between October 1997 and August 2013 were identified from an international, multi-institutional database.ROS1rearrangement was evaluated by break-apart fluorescencein situhybridization using tissue microarrays of these patients.


RESULTS
Of 261 CCA evaluated, three cases (1.1%) showedROS1rearrangement by fluorescencein situhybridization (FISH), all of which were derived from intrahepatic origin. ROS1 protein expression was observed in 38 samples (19.1%). Significantly larger tumor size was observed in ROS1 immunohistochemistry (IHC)-negative patients compared with ROS1 IHC-positive patients.ROS1FISH-positive patients had a single tumor with a median size of 4 cm and well-to-moderate differentiation. Overall, there was no difference in terms of baseline characteristics, overall survival, and recurrence-free survival betweenROS1-positive and -negative patients.


CONCLUSIONS
ROS1rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Sun Min
SM
Lim
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Jeong Eun
JE
Yoo
Department of Pathology, Singapore General Hospital, Singapore.
Kiat Hon
KH
Lim
Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
David Wai
DW
Meng Tai
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Byoung Chul
BC
Cho
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.|BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea.
Young Nyun
YN
Park
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D005260:Female; D015321:Gene Rearrangement; D056726:Genetic Association Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
Cholangiocarcinoma; Fluorescent in situ hybridization; ROS1