Intended for European healthcare professionals only
Intended for European healthcare professionals only
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Genomic testing in intrahepatic cholangiocarcinoma (iCCA)

The introduction of next-generation sequencing (NGS) technologies has opened new horizons for a better understanding of the molecular basis of cholangiocarcinoma (CCA), and for the identification and evaluation of potential new treatments tailored to the molecular characteristics of patients’ tumours1

The high frequency of potentially targetable genomic alterations in iCCA strongly supports the need for molecular profiling2

Importance of molecular testing in CCA

Watch the animated video for an overview of the importance of molecular testing from the perspective of a patient and oncologist

Methodology matters

A variety of molecular profiling methods are now available, with NGS and fluorescence in situ hybridisation (FISH) among the most common assays3,4

There are some important differences between the 2 methods:


NGS allows the opportunity, in a molecular target-rich disease like iCCA, to analyse a tissue sample for multiple alterations at the same time. Therefore, although the specimen size for NGS is initially larger and the turnaround time may be longer, it may preclude the need for further biopsies for the purposes of molecular testing5-7


FISH was originally designed to identify 1 specific, predetermined alteration at a time. Although more recent FISH assays can detect multiple prespecified genetic alterations, NGS can provide additional information not possible through FISH3,4

The European Society for Medical Oncology (ESMO) recommends routine use of multigene NGS to detect level I genomic alterations (IDH1 mutations, FGFR2 fusions, NTRK fusions and MSI-H) in advanced CCA8

Biopsy technique

Biopsy technique should account for planned molecular profiling as well as diagnostic needs

Compared with the tissue required for a histological diagnosis, additional tissue may be required to satisfy emerging molecular profiling needs in iCCA12,13

A molecular profiling plan should be considered early on, including tissue requirements for the specific planned biomarker test when determining biopsy technique12,13

Although more invasive than fine-needle aspiration, core-needle biopsy provides important pathological details about the tumour and typically yields enough tissue to allow for comprehensive molecular profiling12-14

Key differences in biopsy techniques

Core-needle biopsy12-14 Fine-needle aspiration12


  • Acquires more tissue
    • Allows for additional histological and immunohistochemical testing
    • Allows for more comprehensive molecular profiling
  • Acquires more structured tissue
    • Provides information on cytology and tissue architecture


  • Less invasive
  • Results can be obtained quickly
  • May be associated with fewer complications


  • More invasive


  • Acquires limited amount of tissue, which does not allow for further testing or comprehensive molecular profiling

Once the biopsy is performed, the tissue should be processed promptly and prepared according to the specific needs of the molecular profiling assay selected5

Liquid biopsy

Compared to traditional tissue sampling methods, liquid biopsy is less invasive and can be serially repeated, allowing real-time monitoring of the tumour genomic profile and/or response to therapy15

Diagnostic biomarkers and potential therapeutic targets can be detected by analysing cellular components such as cell-free DNA (cfDNA), circulating tumour DNA (ctDNA), proteins, cytokines and serum metabolites15

Analysis of cfDNA/ctDNA via NGS has identified a range of genomic alterations in patients with biliary tract tumours, including TP53, BRAF, FGFR2 and IDHA1 mutations, ERBB2 amplifications and FGFR2 fusions15

However, the role of liquid biopsy in clinical practice for patients with cholangiocarcinoma is still marginal and further research is necessary15

A multidisciplinary approach to unresectable or metastatic iCCA may enable a more comprehensive understanding of disease biology and treatment options16
REFERENCES: 1. Simile MM, et al. Medicina (Kaunas). 2019;55:42. 2. Lowery MA, et al. Clin Cancer Res. 2018;24:4154–61. 3. Dudley JC, et al. J Mol Diagn. 2016;18:124–30. 4. Hu L, et al. Biomark Res. 2014;2:3. 5. Cree IA, et al. J Clin Pathol. 2014;67:923–31. 6. Damodaran S, et al. Am Soc Clin Oncol Educ Book. 2015;e175–e182. 7. Su D, et al. J Exp Clin Cancer Res. 2017;36:121. 8. Mosele F, et al. Ann Oncol. 2020;31:1491–505. 9. Jain A, et al. JCO Precis Oncol. 2018;2:1–12. 10. Silverman IM, et al. Cancer Discov. 2021;11:326–39. 11. Barr FG. Expert Rev Mol Diagn. 2016;16:921–3. 12. Wee A. J Gastrointest Oncol. 2013;4:5–7. 13. Stewart CJR, et al. J Clin Pathol. 2002;55:93–7. 14. International Consensus Group for Hepatocellular Neoplasia. Hepatology; 2009;49:658–64. 15. Rompianesi G, et al. World J Gastrointest Oncol. 2021;13:332–50. 16. Patel T. Nat Rev Gastroenterol Hepatol. 2011;8:189–200.
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