Rare Incidence of ROS1 Rearrangement in Cholangiocarcinoma
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose The recent discovery and characterization of an oncogenic ROS1 gene 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 with ROS1 rearrangement in patients with cholangiocarcinoma (CCA). Materials and 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. ROS1 rearrangement was evaluated by break-apart fluorescence in situ hybridization using tissue microarrays of these patients. Results Of 261 CCA evaluated, three cases (1.1%) showed ROS1 rearrangement by fluorescence in situ hybridization (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. ROS1 FISH–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 between ROS1-positive and -negative patients. Conclusion ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.
Abstract
Purpose The recent discovery and characterization of an oncogenic ROS1 gene 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 with ROS1 rearrangement in patients with cholangiocarcinoma (CCA). Materials and 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. ROS1 rearrangement was evaluated by break-apart fluorescence in situ hybridization using tissue microarrays of these patients. Results Of 261 CCA evaluated, three cases (1.1%) showed ROS1 rearrangement by fluorescence in situ hybridization (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. ROS1 FISH–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 between ROS1-positive and -negative patients. Conclusion ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.
참고문헌 (20)
- Razumilava N, "Cholangiocarcinoma", Lancet, 383, pp.2168~2179 (2014)
- Everhart JE, "Burden of digestive diseases in the United States Part III : liver, biliary tract, and pancreas", Gastroenterology, 136, pp.1134~1144 (2009)
- Khan SA, "Guidelines for the diagnosis and treatment of cholangiocarcinoma : an update", Gut, 61, pp.1657~1669 (2012)
- Summersgill BM, "Fluorescence in situ hybridization analysis of formalin fixed paraffin embedded tissues, including tissue microarrays", Methods Mol Biol, 659, pp.51~70 (2010)
- Rosen CB, "Liver transplantation for cholangiocarcinoma", Transpl Int, 23, pp.692~697 (2010)
- Valle J, "Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer", N Engl J Med, 362, pp.1273~1281 (2010)
- Zabron A, "The challenge of cholangiocarcinoma : dissecting the molecular mechanisms of an insidious cancer", Dis Model Mech, 6, pp.281~292 (2013)
- Ong CK, "Exome sequencing of liver fluke-associated cholangiocarcinoma", Nat Genet, 44, pp.690~693 (2012)
- Lee J, "Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer : a multicentre, open-label, randomised, phase 3 study", Lancet Oncol, 13, pp.181~188 (2012)
- Gu TL, "Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma", PLoS One, 6, pp.e15640~ (2011)
- Saborowski A, "Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target", Proc Natl Acad Sci U S A, 110, pp.19513~19518 (2013)
- Bergethon K, "ROS1 rearrangements define a unique molecular class of lung cancers", J Clin Oncol, 30, pp.863~870 (2012)
- Sharma S, "Characterization of the ros1-gene products expressed in human glioblastoma cell lines", Oncogene Res, 5, pp.91~100 (1989)
- Kim HR, "The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma", Ann Oncol, 24, pp.2364~2370 (2013)
- Chin LP, "Targeting ROS1 with anaplastic lymphoma kinase inhibitors : a promising therapeutic strategy for a newly defined molecular subset of non-smallcell lung cancer", J Thorac Oncol, 7, pp.1625~1630 (2012)
- Ou SH, "ROS1 as a 'druggable' receptor tyrosine kinase : lessons learned from inhibiting the ALK pathway", Expert Rev Anticancer Ther, 12, pp.447~456 (2012)
- Shaw AT, "Crizotinib in ROS1-rearranged non-small-cell lung cancer", N Engl J Med, 371, pp.1963~1971 (2014)
- Arai Y, "Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma", Hepatology, 59, pp.1427~1434 (2014)
- Davies KD, "Identifying and targeting ROS1 gene fusions in non-small cell lung cancer", Clin Cancer Res, 18, pp.4570~4579 (2012)
- Lee KH, "Clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma", BMC Cancer, 15, pp.721~ (2015)