Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma

Rondell P. Graham, Emily G. Barr Fritcher, Ekaterina Pestova, John Schulz, Leonid A. Sitailo, George Vasmatzis, Stephen J. Murphy, Robert R. McWilliams, Steven N. Hart, Kevin C. Halling, Lewis R. Roberts, Gregory J. Gores, Fergus J. Couch, Lizhi Zhang, Mitesh J. Borad, Benjamin R. Kipp

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Patients with cholangiocarcinoma often present with locally advanced or metastatic disease. There is a need for effective therapeutic strategies for advanced stage cholangiocarcinoma. Recently, FGFR2 translocations have been identified as a potential target for tyrosine kinase inhibitor therapies. This study evaluated 152 cholangiocarcinomas and 4 intraductal papillary biliary neoplasms of the bile duct for presence of FGFR2 translocations by fluorescence in situ hybridization and characterized the clinicopathologic features of cases with FGFR2 translocations. Thirteen (10 women, 3 men; 8%) of 156 biliary tumors harbored FGFR2 translocations, including 12 intrahepatic cholangiocarcinomas (12/96; 13%) and 1 intraductal papillary neoplasm of the bile duct. Histologically, cholangiocarcinomas with FGFR2 translocations displayed prominent intraductal growth (62%) or anastomosing tubular glands with desmoplasia (38%). Immunohistochemically, the tumors with FGFR2 translocations frequently showed weak and patchy expression of CK19 (77%). Markers of the stem cell phenotype in cholangiocarcinoma, HepPar1 and CK20, were negative in all cases. The median cancer-specific survival for patients whose tumors harbored FGFR2 translocations was 123 months compared to 37 months for cases without FGFR2 translocations (P =.039). This study also assessed 100 cholangiocarcinomas for ERBB2 amplification and ROS1 translocations. Of the cases tested, 3% and 1% were positive for ERBB2 amplification and ROS1 translocation, respectively. These results confirm that FGFR2, ERRB2, and ROS1 alterations are potential therapeutic targets for intrahepatic cholangiocarcinoma.

Original languageEnglish (US)
Pages (from-to)1630-1638
Number of pages9
JournalHuman Pathology
Volume45
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Bile
  • ERBB2
  • FGFR2
  • HER2
  • ROS1
  • Targeted therapy
  • Tyrosine kinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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