Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted...

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Bibliographic Details
Published in:Cancers 2021-12, Vol.13 (23), p.6049
Main Authors: Gruttadauria, Salvatore, Barbera, Floriana, Pagano, Duilio, Liotta, Rosa, Miraglia, Roberto, Barbara, Marco, Bavetta, Maria Grazia, Cammà, Calogero, Petridis, Ioannis, Di Carlo, Daniele, Conaldi, Pier Giulio, Di Francesco, Fabrizio
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Biopsy
Cancer therapies
Chemotherapy
Cholangiocarcinoma
Chromatin remodeling
Epigenetics
Genes
Genomics
Liver diseases
Liver transplantation
MAP kinase
Mortality
Mutation
Next-generation sequencing
p53 Protein
Patients
Signal transduction
Software
Solid tumors
TOR protein
Transplants & implants
Tumorigenesis
Tumors
Wnt protein
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Summary:Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted to this disease and some evidence supports liver transplantation (LT) as an appropriate treatment for intrahepatic cholangiocarcinoma; evolving work has also provided a framework for better understanding the genetic basis of this cancer. The aim of this study was to provide a clinical description of our series of patients complemented with Next-Generation Sequencing genomic profiling. From 1999 to 2021, 12 patients who underwent LT with either iCCA or a combined hepatocellular and cholangiocellular carcinoma (HCC-iCCA) were included in this study. Mutations were observed in gene activating signaling pathways known to be involved with iCCA tumorigenesis (KRAS/MAPK, P53, PI3K-Akt/mTOR, cAMP, WNT, epigenetic regulation and chromatin remodeling). Among several others, a strong association was observed between the Notch pathway and tumor size (point-biserial rhopb = 0.93). Our results are suggestive of the benefit potentially derived from molecular analysis to improve our diagnostic capabilities and to devise new treatment protocols, and eventually ameliorate long-term survival of patients affected by iCCA or HCC-iCCA.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13236049