Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Solidité :
Doit faire évoluer notre pratique :
Dans certains cas
Nom du veilleur :
Professeur Sylvain MANFREDI
Coup de coeur :
British journal of Cancer
  2019 Jan;120(1):109-114.  
  doi: 10.1038/s41416-018-0199-2.  
  Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma  
  Goeppert B, Roessler S, Renner M, Singer S, Mehrabi A, Vogel MN, Pathil A, Czink E, Köhler B, Springfeld C, Pfeiffenberger J, Rupp C, Weiss KH, Schirmacher P, von Knebel Doeberitz M, Kloor M  



A major molecular pathway of genetic instability in cancer is DNA mismatch repair deficiency. High-level microsatellite instability (MSI-H) is currently the best predictor of responsiveness towards immune checkpoint blockade. Data about the prevalence of high-level microsatellite instability in cholangiocarcinoma (CCA) has been conflicting.


We employed a cohort comprising 308 Western-world, non-liver fluke-associated CCAs (159 intrahepatic, 106 perihilar, and 43 distal). We analysed the mononucleotide microsatellite instability marker panel consisting of BAT25, BAT26, and CAT25 and detected MSI-H in 4/308 CCAs (1.3%).


Patients affected by MSI-H CCA had mostly an atypical histomorphology (p = 0.004), showed a longer overall survival, although having a high tumour stage, and were of younger age. Correlation analysis of microsatellite instability status with tumour-infiltrating immune cells, MHC I, and PD-L1 expression in the same cholangiocarcinoma cohort showed higher numbers of CD8 + T cells, FOXP3 + regulatory T cells, CD20 + B cells and high or at least moderate MHC I expression levels in MSI-H CCAs.


Even though the overall number of MSI-H CCAs is low, the dismal prognosis of the disease and the therapeutic option of immune checkpoint blockade in the respective patients justify MSI testing of cholangiocarcinoma, particularly in younger patients showing an atypical histomorphology.


Question posée
Caractérisation des cholangiocarcinomes MSI. Données de cohorte.
Question posée
Les cholangiocarcinomes MSI sont associés à une histologie atypique, intéressent plus souvent des sujets jeunes, ont un meilleur pronostic et sont de bon candidats à l’immunothérapie.

Situation rare, à ne pas manquer.