Pedro Luiz Serrano Uson Junior1,2, Thomas T DeLeon1, James M Bogenberger1, Rish K Pai3, Heidi E Kosiorek4, Jun Yin5, Daniel H Ahn1, Mohammad Bassam Sonbol1, Tanios Bekaii-Saab1, Aaron S Mansfield6,7, Kenneth Buetow8, Gregory J Gores9, Rory Smoot6, George Vasmatzis10, Benjamin R Kipp11, Amit Mahipal6, Alexander T Baker1, Hani Babiker12, Oumar Barro1, Chelsae Dumbauld1, Yumei Zhou1, Faaiq N Aslam13, Michael Barrett7, Bertram Jacobs8, Nathalie Meurice1, Mansi Arora1, Joachim Petit1, Natalie Elliott1, Bolni Nagalo1,14, Marcela A Salomao3, Mitesh J Borad15,16,17,18. 1. Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA. 2. Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. 3. Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA. 4. Department of Health Sciences Research, Section of Biostatistics, Mayo Clinic, Scottsdale, AZ, USA. 5. Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA. 6. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA. 7. Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. 8. Arizona State University, Tempe, AZ, USA. 9. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rochester, MN, USA. 10. Department of Molecular Medicine, Rochester, MN, USA. 11. Division of Anatomic Pathology and Laboratory Medicine, Department of Pathology, Mayo Clinic, Rochester, MN, USA. 12. Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA. 13. Mayo Clinic School of Medicine, Scottsdale, AZ, USA. 14. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 15. Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA. Borad.Mitesh@Mayo.edu. 16. Department of Molecular Medicine, Rochester, MN, USA. Borad.Mitesh@Mayo.edu. 17. Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. Borad.Mitesh@Mayo.edu. 18. Mayo Clinic Cancer Center, 5777 E Mayo Blvd, Phoenix, AZ, USA. Borad.Mitesh@Mayo.edu.
Abstract
BACKGROUND: FGFR2 genomic alterations are observed in 10-20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized. AIMS: To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations. METHODS: FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR). RESULTS: Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining. CONCLUSION: FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations.
BACKGROUND: FGFR2 genomic alterations are observed in 10-20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized. AIMS: To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations. METHODS: FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR). RESULTS: Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining. CONCLUSION: FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations.
Authors: Rachna T Shroff; Erin B Kennedy; Melinda Bachini; Tanios Bekaii-Saab; Christopher Crane; Julien Edeline; Anthony El-Khoueiry; Mary Feng; Matthew H G Katz; John Primrose; Heloisa P Soares; Juan Valle; Shishir K Maithel Journal: J Clin Oncol Date: 2019-03-11 Impact factor: 50.717