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FGFR2-IIIb Expression by Immunohistochemistry Has High Specificity in Cholangiocarcinoma with FGFR2 Genomic
Pedro Luiz Serrano Uson Junior1,2, Thomas T DeLeon1, James M Bogenberger1
1Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA.
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.
Insights
FGFR2 protein expression via immunohistochemistry is highly specific for detecting FGFR2 genomic alterations in cholangiocarcinoma (CCA). A positive test implies alterations, but a negative test requires further molecular testing (NGS or FISH).
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- FGFR2 genomic alterations occur in 10-20% of cholangiocarcinoma (CCA).
- FGFR2 fusions are actionable targets, but protein expression is not well-characterized.
Purpose of the Study:
- To evaluate FGFR2 protein expression in CCA with FGFR2 genomic alterations.
- To determine the diagnostic accuracy of FGFR2 immunohistochemistry (IHC) for detecting genomic alterations.
- To assess the correlation between FGFR2 expression and clinical outcomes.
Main Methods:
- Evaluated FGFR2 protein expression in 99 CCA cases using two antibodies via IHC.
- Confirmed FGFR2 genomic alterations using next-generation sequencing (NGS) or fluorescence in situ hybridization (FISH).
- Assessed IHC specificity, sensitivity, and correlation with overall survival, progression-free survival, and time-to-tumor recurrence.
Main Results:
- IHC with two antibodies demonstrated high specificity (82.9% and 97.7%) and moderate sensitivity (53.9% and 57.1%) for detecting FGFR2 genomic alterations.
- No significant differences in overall survival, progression-free survival, or time-to-tumor recurrence were observed between patients with positive or negative FGFR2 staining.
Conclusions:
- FGFR2 IHC is highly specific for implying FGFR2 genomic alterations in CCA.
- A positive IHC result suggests genomic alterations, while a negative result necessitates NGS or FISH confirmation.
