Low frequency of mismatch repair deficiency in gallbladder cancer.
Adenocarcinoma
/ diagnosis
Aged
Brain Neoplasms
/ diagnosis
Cohort Studies
Colorectal Neoplasms
/ diagnosis
DNA Mismatch Repair
Female
Gallbladder Neoplasms
/ diagnosis
Humans
Immunohistochemistry
Male
Microsatellite Instability
MutL Protein Homolog 1
/ genetics
Neoplastic Syndromes, Hereditary
/ diagnosis
Phenotype
Biliary tract cancer
DNA mismatch repair deficiency
Gallbladder cancer
Microsatellite instability
Journal
Diagnostic pathology
ISSN: 1746-1596
Titre abrégé: Diagn Pathol
Pays: England
ID NLM: 101251558
Informations de publication
Date de publication:
08 May 2019
08 May 2019
Historique:
received:
09
12
2018
accepted:
16
04
2019
entrez:
10
5
2019
pubmed:
10
5
2019
medline:
26
11
2019
Statut:
epublish
Résumé
DNA mismatch repair (MMR) deficiency is a major pathway of genomic instability in cancer. It leads to the accumulation of numerous mutations predominantly at microsatellite sequences, a phenotype known as microsatellite instability (MSI). MSI tumors have a distinct clinical behavior and commonly respond well to immune checkpoint blockade, irrespective of their origin. Data about the prevalence of MSI among gallbladder cancer (GBC) have been conflicting. We here analyzed a well-characterized cohort of 69 Western-world GBCs. We analyzed the mononucleotide MSI marker panel consisting of BAT25, BAT26, and CAT25 to determine the prevalence of MMR deficiency-induced MSI. MSI was detected in 1/69 (1.4%) of analyzed GBCs. The detected MSI GBC had a classical histomorphology, i.e. of acinar/tubular/glandular pancreatobiliary phenotype, and showed nuclear expression of all four MMR proteins MLH1, MSH2, MSH6, and PMS2. The MSI GBC patient showed a prolonged overall survival, despite having a high tumor stage at diagnosis. The patient had no known background or family history indicative of Lynch syndrome. Even though the overall number of MSI tumors is low in GBC, the potentially therapeutic benefit of checkpoint blockade in the respective patients may justify MSI analysis of GBC.
Sections du résumé
BACKGROUND
BACKGROUND
DNA mismatch repair (MMR) deficiency is a major pathway of genomic instability in cancer. It leads to the accumulation of numerous mutations predominantly at microsatellite sequences, a phenotype known as microsatellite instability (MSI). MSI tumors have a distinct clinical behavior and commonly respond well to immune checkpoint blockade, irrespective of their origin. Data about the prevalence of MSI among gallbladder cancer (GBC) have been conflicting. We here analyzed a well-characterized cohort of 69 Western-world GBCs.
METHODS
METHODS
We analyzed the mononucleotide MSI marker panel consisting of BAT25, BAT26, and CAT25 to determine the prevalence of MMR deficiency-induced MSI.
RESULTS
RESULTS
MSI was detected in 1/69 (1.4%) of analyzed GBCs. The detected MSI GBC had a classical histomorphology, i.e. of acinar/tubular/glandular pancreatobiliary phenotype, and showed nuclear expression of all four MMR proteins MLH1, MSH2, MSH6, and PMS2. The MSI GBC patient showed a prolonged overall survival, despite having a high tumor stage at diagnosis. The patient had no known background or family history indicative of Lynch syndrome.
CONCLUSIONS
CONCLUSIONS
Even though the overall number of MSI tumors is low in GBC, the potentially therapeutic benefit of checkpoint blockade in the respective patients may justify MSI analysis of GBC.
Identifiants
pubmed: 31068195
doi: 10.1186/s13000-019-0813-5
pii: 10.1186/s13000-019-0813-5
pmc: PMC6506936
doi:
Substances chimiques
MLH1 protein, human
0
MutL Protein Homolog 1
EC 3.6.1.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
36Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB/TR 209
Organisme : European Union Horizon 2020
ID : 667273
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