Abstract：
BACKGROUND: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. METHODS: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%). RESULTS: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. CONCLUSIONS: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.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
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 Mdoi
10.1038/s41416-018-0199-2subject
Has Abstractpub_date
2019-01-01 00:00:00pages
109-114issue
1eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0199-2journal_volume
120pub_type
杂志文章abstract：:'de novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of...
journal_title：British journal of cancer
pub_type： 杂志文章
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pub_type： 临床试验,杂志文章,随机对照试验
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pub_type： 杂志文章
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doi：10.1038/sj.bjc.6601955
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journal_title：British journal of cancer
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doi：10.1038/bjc.1990.409
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pub_type： 杂志文章,评审
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更新日期：2016-05-24 00:00:00
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pub_type： 杂志文章
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doi：10.1038/sj.bjc.6603483
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doi：10.1038/bjc.2011.23
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pub_type： 杂志文章
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