FGFR mRNA Expression in Cholangiocarcinoma and Its Correlation with FGFR2 Fusion Status and Immune Signatures Article Swipe
Vishwajith Sridharan
,
Azfar Neyaz
,
Abhijit Chogule
,
Islam Baiev
,
Stephanie Reyes
,
Emily G. Barr Fritcher
,
Jochen K. Lennerz
,
William R. Sukov
,
Benjamin R. Kipp
,
David T. Ting
,
Vikram Deshpande
,
Lipika Goyal
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.ccr-22-1244
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.ccr-22-1244
Purpose: Selective FGFR inhibitors are effective against cholangiocarcinomas that harbor gene alterations in FGFR2. Clinical trials suggest that expression of wild-type FGFR mRNA can predict sensitivity to FGFR inhibitors, but this biomarker has not been well characterized in cholangiocarcinoma. This study explores the prevalence of FGFR mRNA overexpression in cholangiocarcinoma, its role in predicting sensitivity to FGFR inhibitors, and its association with immune markers. Experimental Design: Tissue microarrays of intrahepatic (ICC) and extrahepatic cholangiocarcinomas (ECC) resected between 2004 and 2015 were used to evaluate FGFR1–4 mRNA expression levels by RNA in situ hybridization (ISH). Expression levels of FGFR2 mRNA were correlated with FGFR2 fusion status and with patient outcomes. Immune markers expression was assessed by IHC and CSF1 and CSF1 receptor expression were examined by RNA ISH. Results: Among 94 patients with resected cholangiocarcinoma, the majority had ICC (77%). FGFR2 fusions were identified in 23% of ICCs and 5% of ECCs. High levels of FGFR mRNA in FGFR2 fusion–negative ICC/ECC were seen for: FGFR1 (ICC/ECC: 15%/0%), FGFR2 (ICC/ECC: 57%/0%), FGFR3 (ICC/ECC: 53%/18%), and FGFR4 (ICC/ECC: 32%/0%). Overall, 62% of fusion-negative cholangiocarcinomas showed high levels of FGFR mRNA. In patients with advanced FGFR2 fusion–positive ICC, high levels of FGFR2 mRNA did not correlate with clinical benefit. FGFR2 fusion–positive tumors showed a paucity of PD-L1 on tumor cells. Conclusions: FGFR mRNA overexpression occurs frequently in cholangiocarcinoma in the absence of genetic alterations in FGFR. This study identifies a molecular subpopulation in cholangiocarcinoma for which further investigation of FGFR inhibitors is merited outside currently approved indications.
Related Topics
Concepts
Fibroblast growth factor receptor
Immunohistochemistry
Fibroblast growth factor receptor 1
Intrahepatic Cholangiocarcinoma
Messenger RNA
Cancer research
Biology
Tissue microarray
Medicine
Pathology
Internal medicine
Receptor
Fibroblast growth factor
Gene
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1158/1078-0432.ccr-22-1244
- https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-22-1244/3220120/ccr-22-1244.pdf
- OA Status
- hybrid
- Cited By
- 12
- References
- 34
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4300690203
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4300690203Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/1078-0432.ccr-22-1244Digital Object Identifier
- Title
-
FGFR mRNA Expression in Cholangiocarcinoma and Its Correlation with FGFR2 Fusion Status and Immune SignaturesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-10-03Full publication date if available
- Authors
-
Vishwajith Sridharan, Azfar Neyaz, Abhijit Chogule, Islam Baiev, Stephanie Reyes, Emily G. Barr Fritcher, Jochen K. Lennerz, William R. Sukov, Benjamin R. Kipp, David T. Ting, Vikram Deshpande, Lipika GoyalList of authors in order
- Landing page
-
https://doi.org/10.1158/1078-0432.ccr-22-1244Publisher landing page
- PDF URL
-
https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-22-1244/3220120/ccr-22-1244.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-22-1244/3220120/ccr-22-1244.pdfDirect OA link when available
- Concepts
-
Fibroblast growth factor receptor, Immunohistochemistry, Fibroblast growth factor receptor 1, Intrahepatic Cholangiocarcinoma, Messenger RNA, Cancer research, Biology, Tissue microarray, Medicine, Pathology, Internal medicine, Receptor, Fibroblast growth factor, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
12Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 2, 2023: 6Per-year citation counts (last 5 years)
- References (count)
-
34Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| primary_location.landing_page_url | https://doi.org/10.1158/1078-0432.ccr-22-1244 |
| publication_date | 2022-10-03 |
| publication_year | 2022 |
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