FGFR2-IIIb Expression by Immunohistochemistry Has High Specificity in Cholangiocarcinoma with FGFR2 Genomic Alterations.

Autor: Uson Junior PLS; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA.; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil., DeLeon TT; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Bogenberger JM; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Pai RK; Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA., Kosiorek HE; Department of Health Sciences Research, Section of Biostatistics, Mayo Clinic, Scottsdale, AZ, USA., Yin J; Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA., Ahn DH; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Sonbol MB; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Bekaii-Saab T; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Mansfield AS; Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA., Buetow K; Arizona State University, Tempe, AZ, USA., Gores GJ; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rochester, MN, USA., Smoot R; Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA., Vasmatzis G; Department of Molecular Medicine, Rochester, MN, USA., Kipp BR; Division of Anatomic Pathology and Laboratory Medicine, Department of Pathology, Mayo Clinic, Rochester, MN, USA., Mahipal A; Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA., Baker AT; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Babiker H; Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA., Barro O; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Dumbauld C; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Zhou Y; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Aslam FN; Mayo Clinic School of Medicine, Scottsdale, AZ, USA., Barrett M; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA., Jacobs B; Arizona State University, Tempe, AZ, USA., Meurice N; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Arora M; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Petit J; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Elliott N; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA., Nagalo B; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA.; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Salomao MA; Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA., Borad MJ; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA. Borad.Mitesh@Mayo.edu.; Department of Molecular Medicine, Rochester, MN, USA. Borad.Mitesh@Mayo.edu.; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. Borad.Mitesh@Mayo.edu.; Mayo Clinic Cancer Center, 5777 E Mayo Blvd, Phoenix, AZ, USA. Borad.Mitesh@Mayo.edu.
Jazyk: angličtina
Zdroj: Digestive diseases and sciences [Dig Dis Sci] 2022 Aug; Vol. 67 (8), pp. 3797-3805. Date of Electronic Publication: 2021 Nov 13.
DOI: 10.1007/s10620-021-07303-9
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE